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Two-thirds with microscopic colitis respond to bile acid sequestrants
, based on a recent retrospective study from the Mayo Clinic.
The findings support use of BAS in patients with microscopic colitis who fail first-line therapy, or have intolerance to those agents, wrote researchers who were led by Darrell S. Pardi, MD, AGAF, a gastroenterologist with Mayo Clinic, Rochester, Minn. To date, the American Gastroenterological Association (AGA) has refrained from issuing any recommendations for BAS monotherapy in microscopic colitis (MC), the study authors wrote, citing a lack of relevant data.
The AGA recommends budesonide as first-line therapy for patients with moderate to severe symptoms of microscopic colitis. However, the treatment is associated with a high rate of relapse (40%-81%) once the patient stops taking the drug. Its long-term use is associated with a risk of side effects.
“At present, there are no randomized controlled trials that have evaluated the efficacy of BAS monotherapy for MC,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Studies investigating the role of BAM [bile acid malabsorption] in MC are comprised of small cohorts and have shown inconsistent results. Patients without BAM may also respond to BAS therapy. Therefore, the role of BAM and treatment with BAS in MC merits further investigation.”
The study analyzed data from 282 patients (88.3% women) with microscopic colitis treated between 2010 to 2020. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing. After a median follow-up of 4.5 years, cholestyramine was the most prescribed BAS (64.9%), followed by colesevelam (21.6%) and colestipol (13.5%). Approximately half of the patients achieved a complete response (49.3%), while 16.3% had a partial response. Nonresponders accounted for 24.8% of the population, and 9.6% of patients did not tolerate BAS therapy. These outcomes were not significantly impacted by BAS dose or combination with other agents. Additional logistic regression analysis revealed no predictors of response.
After discontinuing BAS, 41.6% of patients had recurrence in a median of 21 weeks, ranging from 1 to 172 weeks.
“Consistent with prior studies evaluating the clinical course of MC and similar to the high rate of recurrence after discontinuation of budesonide, relapse was common after cessation of BAS therapy,” the investigators noted.
Still, the findings suggest that BAS is a valid second-line option with a favorable risk-benefit profile, and an elevated dose appears unnecessary to achieve clinical response.
“These results suggest that BAS may be considered as a treatment option in those that do not respond to first-line options or have intolerance to these agents,” the researchers wrote.
They suggested that BAS may be particularly useful as long-term maintenance therapy for patients wishing to avoid prolonged corticosteroid exposure.
“However, BAS have the potential to interfere with the administration and absorption of other medications, particularly in older populations with polypharmacy,” the researchers wrote. “Patients should thus be closely monitored for drug interactions, especially those taking concurrent medications. BAS should be administered separately from other medications to avoid the potential for drug interactions.”
Ideally, prospective studies will be conducted to confirm these findings, and to identify the subset of patients who are most likely to respond to BAS, the investigators concluded.
Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda; and has consulted for Vedanta, Seres, Phantom Pharmaceuticals, Abbvie, Immunic, and Otsuka.
Despite being increasingly recognized and diagnosed, there remains a scantiness of studies addressing therapeutic options in microscopic colitis (MC). Oral budesonide is recommended as first-line option; however, there is a high relapse rate after budesonide discontinuation, some patients are intolerant, and there is concern for steroid toxicity associated with long-term exposure.
While the cause of MC remains elusive, there is a rationale to suggest that bile acids may play a role in disease pathogenesis. Not only are BA important signaling molecules, acting in inflammation and metabolism, but also prior small studies reported on BA malabsorption co-existing in MC, with variable response rates to BA sequestrants.
This retrospective large study of 282 patients with MC showed that almost two-thirds of patients will present a complete or partial response to BA sequestrant therapy (cholestyramine, colesevelam, and colestipol). For those that relapsed following BA therapy discontinuation, re-treatment was successful in the majority of cases.
Therapy was well tolerated, however caution is needed, as it can interfere with absorption of other medications, and in the long-term also with fat-soluble vitamins. It remains to be determined which patients could benefit the most from BA therapy, since no predictors of response were identified, nor was response associated with BA malabsorption. Nonetheless, this study shows that BA therapy could be an attractive option for steroid-dependent, steroid refractory or intolerant MC patients potentially worth trying before embarking on immunosuppressive or biological therapy. It also highlights the need for carefully conducted clinical trials exploring other options beyond budesonide for this chronic and debilitating condition.
Joana Torres, MD, PhD, is a consultant gastroenterologist at Hospital Beatriz Angelo and Hospital da Luz in Portugal and assistant professor in Uniersidade de Lisboa, Portugal. She has no conflicts.
Despite being increasingly recognized and diagnosed, there remains a scantiness of studies addressing therapeutic options in microscopic colitis (MC). Oral budesonide is recommended as first-line option; however, there is a high relapse rate after budesonide discontinuation, some patients are intolerant, and there is concern for steroid toxicity associated with long-term exposure.
While the cause of MC remains elusive, there is a rationale to suggest that bile acids may play a role in disease pathogenesis. Not only are BA important signaling molecules, acting in inflammation and metabolism, but also prior small studies reported on BA malabsorption co-existing in MC, with variable response rates to BA sequestrants.
This retrospective large study of 282 patients with MC showed that almost two-thirds of patients will present a complete or partial response to BA sequestrant therapy (cholestyramine, colesevelam, and colestipol). For those that relapsed following BA therapy discontinuation, re-treatment was successful in the majority of cases.
Therapy was well tolerated, however caution is needed, as it can interfere with absorption of other medications, and in the long-term also with fat-soluble vitamins. It remains to be determined which patients could benefit the most from BA therapy, since no predictors of response were identified, nor was response associated with BA malabsorption. Nonetheless, this study shows that BA therapy could be an attractive option for steroid-dependent, steroid refractory or intolerant MC patients potentially worth trying before embarking on immunosuppressive or biological therapy. It also highlights the need for carefully conducted clinical trials exploring other options beyond budesonide for this chronic and debilitating condition.
Joana Torres, MD, PhD, is a consultant gastroenterologist at Hospital Beatriz Angelo and Hospital da Luz in Portugal and assistant professor in Uniersidade de Lisboa, Portugal. She has no conflicts.
Despite being increasingly recognized and diagnosed, there remains a scantiness of studies addressing therapeutic options in microscopic colitis (MC). Oral budesonide is recommended as first-line option; however, there is a high relapse rate after budesonide discontinuation, some patients are intolerant, and there is concern for steroid toxicity associated with long-term exposure.
While the cause of MC remains elusive, there is a rationale to suggest that bile acids may play a role in disease pathogenesis. Not only are BA important signaling molecules, acting in inflammation and metabolism, but also prior small studies reported on BA malabsorption co-existing in MC, with variable response rates to BA sequestrants.
This retrospective large study of 282 patients with MC showed that almost two-thirds of patients will present a complete or partial response to BA sequestrant therapy (cholestyramine, colesevelam, and colestipol). For those that relapsed following BA therapy discontinuation, re-treatment was successful in the majority of cases.
Therapy was well tolerated, however caution is needed, as it can interfere with absorption of other medications, and in the long-term also with fat-soluble vitamins. It remains to be determined which patients could benefit the most from BA therapy, since no predictors of response were identified, nor was response associated with BA malabsorption. Nonetheless, this study shows that BA therapy could be an attractive option for steroid-dependent, steroid refractory or intolerant MC patients potentially worth trying before embarking on immunosuppressive or biological therapy. It also highlights the need for carefully conducted clinical trials exploring other options beyond budesonide for this chronic and debilitating condition.
Joana Torres, MD, PhD, is a consultant gastroenterologist at Hospital Beatriz Angelo and Hospital da Luz in Portugal and assistant professor in Uniersidade de Lisboa, Portugal. She has no conflicts.
, based on a recent retrospective study from the Mayo Clinic.
The findings support use of BAS in patients with microscopic colitis who fail first-line therapy, or have intolerance to those agents, wrote researchers who were led by Darrell S. Pardi, MD, AGAF, a gastroenterologist with Mayo Clinic, Rochester, Minn. To date, the American Gastroenterological Association (AGA) has refrained from issuing any recommendations for BAS monotherapy in microscopic colitis (MC), the study authors wrote, citing a lack of relevant data.
The AGA recommends budesonide as first-line therapy for patients with moderate to severe symptoms of microscopic colitis. However, the treatment is associated with a high rate of relapse (40%-81%) once the patient stops taking the drug. Its long-term use is associated with a risk of side effects.
“At present, there are no randomized controlled trials that have evaluated the efficacy of BAS monotherapy for MC,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Studies investigating the role of BAM [bile acid malabsorption] in MC are comprised of small cohorts and have shown inconsistent results. Patients without BAM may also respond to BAS therapy. Therefore, the role of BAM and treatment with BAS in MC merits further investigation.”
The study analyzed data from 282 patients (88.3% women) with microscopic colitis treated between 2010 to 2020. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing. After a median follow-up of 4.5 years, cholestyramine was the most prescribed BAS (64.9%), followed by colesevelam (21.6%) and colestipol (13.5%). Approximately half of the patients achieved a complete response (49.3%), while 16.3% had a partial response. Nonresponders accounted for 24.8% of the population, and 9.6% of patients did not tolerate BAS therapy. These outcomes were not significantly impacted by BAS dose or combination with other agents. Additional logistic regression analysis revealed no predictors of response.
After discontinuing BAS, 41.6% of patients had recurrence in a median of 21 weeks, ranging from 1 to 172 weeks.
“Consistent with prior studies evaluating the clinical course of MC and similar to the high rate of recurrence after discontinuation of budesonide, relapse was common after cessation of BAS therapy,” the investigators noted.
Still, the findings suggest that BAS is a valid second-line option with a favorable risk-benefit profile, and an elevated dose appears unnecessary to achieve clinical response.
“These results suggest that BAS may be considered as a treatment option in those that do not respond to first-line options or have intolerance to these agents,” the researchers wrote.
They suggested that BAS may be particularly useful as long-term maintenance therapy for patients wishing to avoid prolonged corticosteroid exposure.
“However, BAS have the potential to interfere with the administration and absorption of other medications, particularly in older populations with polypharmacy,” the researchers wrote. “Patients should thus be closely monitored for drug interactions, especially those taking concurrent medications. BAS should be administered separately from other medications to avoid the potential for drug interactions.”
Ideally, prospective studies will be conducted to confirm these findings, and to identify the subset of patients who are most likely to respond to BAS, the investigators concluded.
Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda; and has consulted for Vedanta, Seres, Phantom Pharmaceuticals, Abbvie, Immunic, and Otsuka.
, based on a recent retrospective study from the Mayo Clinic.
The findings support use of BAS in patients with microscopic colitis who fail first-line therapy, or have intolerance to those agents, wrote researchers who were led by Darrell S. Pardi, MD, AGAF, a gastroenterologist with Mayo Clinic, Rochester, Minn. To date, the American Gastroenterological Association (AGA) has refrained from issuing any recommendations for BAS monotherapy in microscopic colitis (MC), the study authors wrote, citing a lack of relevant data.
The AGA recommends budesonide as first-line therapy for patients with moderate to severe symptoms of microscopic colitis. However, the treatment is associated with a high rate of relapse (40%-81%) once the patient stops taking the drug. Its long-term use is associated with a risk of side effects.
“At present, there are no randomized controlled trials that have evaluated the efficacy of BAS monotherapy for MC,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Studies investigating the role of BAM [bile acid malabsorption] in MC are comprised of small cohorts and have shown inconsistent results. Patients without BAM may also respond to BAS therapy. Therefore, the role of BAM and treatment with BAS in MC merits further investigation.”
The study analyzed data from 282 patients (88.3% women) with microscopic colitis treated between 2010 to 2020. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing. After a median follow-up of 4.5 years, cholestyramine was the most prescribed BAS (64.9%), followed by colesevelam (21.6%) and colestipol (13.5%). Approximately half of the patients achieved a complete response (49.3%), while 16.3% had a partial response. Nonresponders accounted for 24.8% of the population, and 9.6% of patients did not tolerate BAS therapy. These outcomes were not significantly impacted by BAS dose or combination with other agents. Additional logistic regression analysis revealed no predictors of response.
After discontinuing BAS, 41.6% of patients had recurrence in a median of 21 weeks, ranging from 1 to 172 weeks.
“Consistent with prior studies evaluating the clinical course of MC and similar to the high rate of recurrence after discontinuation of budesonide, relapse was common after cessation of BAS therapy,” the investigators noted.
Still, the findings suggest that BAS is a valid second-line option with a favorable risk-benefit profile, and an elevated dose appears unnecessary to achieve clinical response.
“These results suggest that BAS may be considered as a treatment option in those that do not respond to first-line options or have intolerance to these agents,” the researchers wrote.
They suggested that BAS may be particularly useful as long-term maintenance therapy for patients wishing to avoid prolonged corticosteroid exposure.
“However, BAS have the potential to interfere with the administration and absorption of other medications, particularly in older populations with polypharmacy,” the researchers wrote. “Patients should thus be closely monitored for drug interactions, especially those taking concurrent medications. BAS should be administered separately from other medications to avoid the potential for drug interactions.”
Ideally, prospective studies will be conducted to confirm these findings, and to identify the subset of patients who are most likely to respond to BAS, the investigators concluded.
Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda; and has consulted for Vedanta, Seres, Phantom Pharmaceuticals, Abbvie, Immunic, and Otsuka.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Low-certainty evidence supports probiotics for IBS
or very low certainty, with many studies suffering from bias, according to a recent review and meta-analysis.
These shortcomings in the probiotic research landscape should be kept in mind when making treatment recommendations, reported researchers who were led by Alexander C. Ford, MBChB, of the Leeds Gastroenterology Institute, University of Leeds (England). They suggested these issues need to be addressed in the methodology of future clinical trials.
“Although multiple probiotics have been tested in IBS in randomized clinical trials, understanding of which probiotics may be beneficial is limited,” the investigators wrote in Gastroenterology.
They noted that previous efforts – including their own – to meta-analyze these findings have been hindered by a scarcity of trial data coupled with heterogeneity across probiotic strains, combinations, and doses, resulting in clinical uncertainty.
“Making recommendations concerning which probiotics, or combinations of probiotics, are beneficial according to IBS subtype or individual symptom has been difficult to date,” they wrote.
To narrow this knowledge gap, the researchers conducted an updated systematic review and meta-analysis with newly identified trials.
“There is continued interest in the role of probiotics in the management of IBS, as evidenced by the publication of more than 20 new randomized clinical trials since the prior version of this meta-analysis in 2018,” they wrote.
The new dataset included 82 RCTs comprising 10,332 patients with IBS. Along with safety, three separate efficacy endpoints were evaluated: global symptoms, abdominal pain, and abdominal bloating or distension.
For global symptoms, moderate-certainty evidence supported the efficacy of Escherichia coli strains; low-certainty data supported Lactobacillus plantarum 299V and other Lactobacillus strains; and very-low-certainty evidence supported Bacillus, LacClean Gold S, and Duolac 7s strains, and combination probiotics.
For abdominal pain, low-certainty evidence supported Bifidobacterium strains and Saccharomyces cerevisiae I-3856. Very-low-certainty data supported Lactobacillus, Saccharomyces, and Bacillus strains, and combination probiotics.
Very-low-certainty evidence supported the benefits of Bacillus strains and combination probiotics for alleviating abdominal bloating or distension.
In a safety analysis of 55 trials involving more than 7,000 patients, risk of adverse events was no higher for probiotics than placebo.
“Our analyses provide some support for the use of certain probiotics in IBS, and also for particular strains for specific symptoms,” the investigators wrote. “However, there is a paucity of data for their use in patients with IBS-C [IBS with constipation], with only seven RCTs reporting efficacy in this subtype, and no evidence of efficacy in any of these analyses. Their use in patients with IBS-C is, therefore, not supported by current evidence.”
A broader discussion in the publication called out the general lack of high certainty evidence in this area of clinical research.
“Only 24 of 82 eligible RCTs were low risk of bias across all domains, and there was significant heterogeneity between trials in many of our analyses, as well as evidence of publication bias, or other small study effects, in some of our analyses,” the researchers wrote. “The fact that few of the included studies were low risk of bias across all domains should be borne in mind when making treatment recommendations.”
The investigators disclosed relationships with Salix, Biocodex, 4D Pharma, and others.
IBS patients frequently inquire about probiotics. As a clinician, this can be difficult to address. A search of the literature yields numerous small trials. Turning to the guidelines does not help, as the AGA Clinical Practice Guidelines on Probiotics offer no recommendations for IBS because of the low quality of evidence. Nevertheless, we have patients who want to try probiotics. Some of these patients have had inadequate responses to first-line therapies and/or prefer a nonpharmacologic approach.
For example, the strain with the most trials was Lactobacillus plantarum 299V. The dose used (10 billion CFU once daily) is commercially available (Jarrow Formulas Ideal Bowel Support® LP299V®). Bacillus strains were also promising for global symptoms, abdominal pain and bloating. Two trials used the same strain and dose, Bacillus coagulans MTCC 5856, 2 billion CFU once daily, also commercially available (LactoSpore). Both can be purchased via major online retailers for $10-$13 for a 30-day supply. I am glad to have something to recommend however conditionally.
Elizabeth (Beth) Videlock, MD, PhD is assistant professor of medicine in the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California, Los Angeles, and a staff physician in gastroenterology in the Greater Los Angeles Veterans Affairs Healthcare System. She is co-lead of the neurodevelopmental and neurodegenerative diseases research program of the Goodman-Luskin Microbiome Center at UCLA. She has no relevant disclosures.
IBS patients frequently inquire about probiotics. As a clinician, this can be difficult to address. A search of the literature yields numerous small trials. Turning to the guidelines does not help, as the AGA Clinical Practice Guidelines on Probiotics offer no recommendations for IBS because of the low quality of evidence. Nevertheless, we have patients who want to try probiotics. Some of these patients have had inadequate responses to first-line therapies and/or prefer a nonpharmacologic approach.
For example, the strain with the most trials was Lactobacillus plantarum 299V. The dose used (10 billion CFU once daily) is commercially available (Jarrow Formulas Ideal Bowel Support® LP299V®). Bacillus strains were also promising for global symptoms, abdominal pain and bloating. Two trials used the same strain and dose, Bacillus coagulans MTCC 5856, 2 billion CFU once daily, also commercially available (LactoSpore). Both can be purchased via major online retailers for $10-$13 for a 30-day supply. I am glad to have something to recommend however conditionally.
Elizabeth (Beth) Videlock, MD, PhD is assistant professor of medicine in the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California, Los Angeles, and a staff physician in gastroenterology in the Greater Los Angeles Veterans Affairs Healthcare System. She is co-lead of the neurodevelopmental and neurodegenerative diseases research program of the Goodman-Luskin Microbiome Center at UCLA. She has no relevant disclosures.
IBS patients frequently inquire about probiotics. As a clinician, this can be difficult to address. A search of the literature yields numerous small trials. Turning to the guidelines does not help, as the AGA Clinical Practice Guidelines on Probiotics offer no recommendations for IBS because of the low quality of evidence. Nevertheless, we have patients who want to try probiotics. Some of these patients have had inadequate responses to first-line therapies and/or prefer a nonpharmacologic approach.
For example, the strain with the most trials was Lactobacillus plantarum 299V. The dose used (10 billion CFU once daily) is commercially available (Jarrow Formulas Ideal Bowel Support® LP299V®). Bacillus strains were also promising for global symptoms, abdominal pain and bloating. Two trials used the same strain and dose, Bacillus coagulans MTCC 5856, 2 billion CFU once daily, also commercially available (LactoSpore). Both can be purchased via major online retailers for $10-$13 for a 30-day supply. I am glad to have something to recommend however conditionally.
Elizabeth (Beth) Videlock, MD, PhD is assistant professor of medicine in the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California, Los Angeles, and a staff physician in gastroenterology in the Greater Los Angeles Veterans Affairs Healthcare System. She is co-lead of the neurodevelopmental and neurodegenerative diseases research program of the Goodman-Luskin Microbiome Center at UCLA. She has no relevant disclosures.
or very low certainty, with many studies suffering from bias, according to a recent review and meta-analysis.
These shortcomings in the probiotic research landscape should be kept in mind when making treatment recommendations, reported researchers who were led by Alexander C. Ford, MBChB, of the Leeds Gastroenterology Institute, University of Leeds (England). They suggested these issues need to be addressed in the methodology of future clinical trials.
“Although multiple probiotics have been tested in IBS in randomized clinical trials, understanding of which probiotics may be beneficial is limited,” the investigators wrote in Gastroenterology.
They noted that previous efforts – including their own – to meta-analyze these findings have been hindered by a scarcity of trial data coupled with heterogeneity across probiotic strains, combinations, and doses, resulting in clinical uncertainty.
“Making recommendations concerning which probiotics, or combinations of probiotics, are beneficial according to IBS subtype or individual symptom has been difficult to date,” they wrote.
To narrow this knowledge gap, the researchers conducted an updated systematic review and meta-analysis with newly identified trials.
“There is continued interest in the role of probiotics in the management of IBS, as evidenced by the publication of more than 20 new randomized clinical trials since the prior version of this meta-analysis in 2018,” they wrote.
The new dataset included 82 RCTs comprising 10,332 patients with IBS. Along with safety, three separate efficacy endpoints were evaluated: global symptoms, abdominal pain, and abdominal bloating or distension.
For global symptoms, moderate-certainty evidence supported the efficacy of Escherichia coli strains; low-certainty data supported Lactobacillus plantarum 299V and other Lactobacillus strains; and very-low-certainty evidence supported Bacillus, LacClean Gold S, and Duolac 7s strains, and combination probiotics.
For abdominal pain, low-certainty evidence supported Bifidobacterium strains and Saccharomyces cerevisiae I-3856. Very-low-certainty data supported Lactobacillus, Saccharomyces, and Bacillus strains, and combination probiotics.
Very-low-certainty evidence supported the benefits of Bacillus strains and combination probiotics for alleviating abdominal bloating or distension.
In a safety analysis of 55 trials involving more than 7,000 patients, risk of adverse events was no higher for probiotics than placebo.
“Our analyses provide some support for the use of certain probiotics in IBS, and also for particular strains for specific symptoms,” the investigators wrote. “However, there is a paucity of data for their use in patients with IBS-C [IBS with constipation], with only seven RCTs reporting efficacy in this subtype, and no evidence of efficacy in any of these analyses. Their use in patients with IBS-C is, therefore, not supported by current evidence.”
A broader discussion in the publication called out the general lack of high certainty evidence in this area of clinical research.
“Only 24 of 82 eligible RCTs were low risk of bias across all domains, and there was significant heterogeneity between trials in many of our analyses, as well as evidence of publication bias, or other small study effects, in some of our analyses,” the researchers wrote. “The fact that few of the included studies were low risk of bias across all domains should be borne in mind when making treatment recommendations.”
The investigators disclosed relationships with Salix, Biocodex, 4D Pharma, and others.
or very low certainty, with many studies suffering from bias, according to a recent review and meta-analysis.
These shortcomings in the probiotic research landscape should be kept in mind when making treatment recommendations, reported researchers who were led by Alexander C. Ford, MBChB, of the Leeds Gastroenterology Institute, University of Leeds (England). They suggested these issues need to be addressed in the methodology of future clinical trials.
“Although multiple probiotics have been tested in IBS in randomized clinical trials, understanding of which probiotics may be beneficial is limited,” the investigators wrote in Gastroenterology.
They noted that previous efforts – including their own – to meta-analyze these findings have been hindered by a scarcity of trial data coupled with heterogeneity across probiotic strains, combinations, and doses, resulting in clinical uncertainty.
“Making recommendations concerning which probiotics, or combinations of probiotics, are beneficial according to IBS subtype or individual symptom has been difficult to date,” they wrote.
To narrow this knowledge gap, the researchers conducted an updated systematic review and meta-analysis with newly identified trials.
“There is continued interest in the role of probiotics in the management of IBS, as evidenced by the publication of more than 20 new randomized clinical trials since the prior version of this meta-analysis in 2018,” they wrote.
The new dataset included 82 RCTs comprising 10,332 patients with IBS. Along with safety, three separate efficacy endpoints were evaluated: global symptoms, abdominal pain, and abdominal bloating or distension.
For global symptoms, moderate-certainty evidence supported the efficacy of Escherichia coli strains; low-certainty data supported Lactobacillus plantarum 299V and other Lactobacillus strains; and very-low-certainty evidence supported Bacillus, LacClean Gold S, and Duolac 7s strains, and combination probiotics.
For abdominal pain, low-certainty evidence supported Bifidobacterium strains and Saccharomyces cerevisiae I-3856. Very-low-certainty data supported Lactobacillus, Saccharomyces, and Bacillus strains, and combination probiotics.
Very-low-certainty evidence supported the benefits of Bacillus strains and combination probiotics for alleviating abdominal bloating or distension.
In a safety analysis of 55 trials involving more than 7,000 patients, risk of adverse events was no higher for probiotics than placebo.
“Our analyses provide some support for the use of certain probiotics in IBS, and also for particular strains for specific symptoms,” the investigators wrote. “However, there is a paucity of data for their use in patients with IBS-C [IBS with constipation], with only seven RCTs reporting efficacy in this subtype, and no evidence of efficacy in any of these analyses. Their use in patients with IBS-C is, therefore, not supported by current evidence.”
A broader discussion in the publication called out the general lack of high certainty evidence in this area of clinical research.
“Only 24 of 82 eligible RCTs were low risk of bias across all domains, and there was significant heterogeneity between trials in many of our analyses, as well as evidence of publication bias, or other small study effects, in some of our analyses,” the researchers wrote. “The fact that few of the included studies were low risk of bias across all domains should be borne in mind when making treatment recommendations.”
The investigators disclosed relationships with Salix, Biocodex, 4D Pharma, and others.
FROM GASTROENTEROLOGY
AGA aims to increase awareness of exocrine pancreatic insufficiency
The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.
“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”
To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
Clinical features and risk factors
The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.
The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.
Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
Diagnostic strategies
The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).
Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.
The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.
“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.
While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
Treatment strategies
Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.
PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.
Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
Surveillance
EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.
The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.
The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.
“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”
To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
Clinical features and risk factors
The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.
The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.
Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
Diagnostic strategies
The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).
Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.
The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.
“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.
While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
Treatment strategies
Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.
PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.
Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
Surveillance
EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.
The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.
The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.
“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”
To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
Clinical features and risk factors
The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.
The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.
Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
Diagnostic strategies
The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).
Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.
The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.
“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.
While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
Treatment strategies
Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.
PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.
Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
Surveillance
EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.
The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.
FROM GASTROENTEROLOGY
AGA issues CPU for CRC screening, postpolypectomy surveillance
Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.
“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.
With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.
To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.
Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.
“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”
The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.
According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.
The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.
“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”
The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.
Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.
“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.
With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.
To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.
Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.
“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”
The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.
According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.
The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.
“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”
The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.
Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.
“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.
With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.
To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.
Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.
“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”
The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.
According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.
The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.
“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”
The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.
FROM GASTROENTEROLOGY
Real-world data confirm efficacy of dupilumab in severe EoE
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA CPU stresses brain-gut aspects of bloating, distention and belching
A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.
The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.
Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”
The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.
For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.
Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.
Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.
When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.
Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.
“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.
For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.
Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.
Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.
A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.
The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.
Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”
The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.
For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.
Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.
Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.
When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.
Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.
“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.
For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.
Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.
Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.
A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.
The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.
Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”
The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.
For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.
Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.
Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.
When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.
Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.
“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.
For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.
Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.
Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.
FROM GASTROENTEROLOGY
Rectal cancer risk is markedly higher at 10 years post colectomy
, shows a Danish population-based cohort study.
These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.
“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.
Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.
The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.
The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.
This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.
Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).
A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).
Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.
The findings should inform surveillance guidelines, they wrote.
“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.
The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
Rectal cancer risk in colectomized IBD patients is poorly understood, and most guidelines do not specify unique surveillance protocols for this subset of patients. As such, gastroenterologists are often left using their best judgement to decide surveillance intervals in this group.
In a Danish population-based cohort study, Akimenko and colleagues identify a markedly increased risk of rectal cancer 10 years after colectomy in patients with a diverted rectum. This risk is 8-fold compared to a matched IBD cohort without colectomy, 10-fold compared to the background population, and is slightly higher in ulcerative colitis than Crohn’s disease. The relative risk is similar to that identified in a Swedish nationwide study.
The study benefits from a large, unselected cohort and its use of a matched IBD population without colectomy. However, it is not sufficiently powered to assess cancer risk in patients with IRA or IPAA, thus limiting its generalizability. The lengthy 40-year inclusion period, while providing strength in numbers, may also impact the study findings, as significant changes have occurred in IBD management during this timeframe.
The authors herald an important reminder that post-colectomy IBD patients are not ‘out of the woods’ with regards to rectal cancer risk. Inconsistency exists amongst providers when it comes to surveillance intervals in these patients.
The study highlights the need for specific surveillance guidelines for this group, particularly in patients with a diverted rectum. Additional studies are needed to assess risk in patients with IRA or IPAA.
Dr. Maté Gergely is an assistant professor of medicine within the division of gastroenterology at Washington University School of Medicine, St. Louis. He has no relevant disclosures.
Rectal cancer risk in colectomized IBD patients is poorly understood, and most guidelines do not specify unique surveillance protocols for this subset of patients. As such, gastroenterologists are often left using their best judgement to decide surveillance intervals in this group.
In a Danish population-based cohort study, Akimenko and colleagues identify a markedly increased risk of rectal cancer 10 years after colectomy in patients with a diverted rectum. This risk is 8-fold compared to a matched IBD cohort without colectomy, 10-fold compared to the background population, and is slightly higher in ulcerative colitis than Crohn’s disease. The relative risk is similar to that identified in a Swedish nationwide study.
The study benefits from a large, unselected cohort and its use of a matched IBD population without colectomy. However, it is not sufficiently powered to assess cancer risk in patients with IRA or IPAA, thus limiting its generalizability. The lengthy 40-year inclusion period, while providing strength in numbers, may also impact the study findings, as significant changes have occurred in IBD management during this timeframe.
The authors herald an important reminder that post-colectomy IBD patients are not ‘out of the woods’ with regards to rectal cancer risk. Inconsistency exists amongst providers when it comes to surveillance intervals in these patients.
The study highlights the need for specific surveillance guidelines for this group, particularly in patients with a diverted rectum. Additional studies are needed to assess risk in patients with IRA or IPAA.
Dr. Maté Gergely is an assistant professor of medicine within the division of gastroenterology at Washington University School of Medicine, St. Louis. He has no relevant disclosures.
Rectal cancer risk in colectomized IBD patients is poorly understood, and most guidelines do not specify unique surveillance protocols for this subset of patients. As such, gastroenterologists are often left using their best judgement to decide surveillance intervals in this group.
In a Danish population-based cohort study, Akimenko and colleagues identify a markedly increased risk of rectal cancer 10 years after colectomy in patients with a diverted rectum. This risk is 8-fold compared to a matched IBD cohort without colectomy, 10-fold compared to the background population, and is slightly higher in ulcerative colitis than Crohn’s disease. The relative risk is similar to that identified in a Swedish nationwide study.
The study benefits from a large, unselected cohort and its use of a matched IBD population without colectomy. However, it is not sufficiently powered to assess cancer risk in patients with IRA or IPAA, thus limiting its generalizability. The lengthy 40-year inclusion period, while providing strength in numbers, may also impact the study findings, as significant changes have occurred in IBD management during this timeframe.
The authors herald an important reminder that post-colectomy IBD patients are not ‘out of the woods’ with regards to rectal cancer risk. Inconsistency exists amongst providers when it comes to surveillance intervals in these patients.
The study highlights the need for specific surveillance guidelines for this group, particularly in patients with a diverted rectum. Additional studies are needed to assess risk in patients with IRA or IPAA.
Dr. Maté Gergely is an assistant professor of medicine within the division of gastroenterology at Washington University School of Medicine, St. Louis. He has no relevant disclosures.
, shows a Danish population-based cohort study.
These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.
“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.
Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.
The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.
The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.
This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.
Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).
A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).
Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.
The findings should inform surveillance guidelines, they wrote.
“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.
The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
, shows a Danish population-based cohort study.
These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.
“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.
Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.
The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.
The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.
This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.
Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).
A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).
Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.
The findings should inform surveillance guidelines, they wrote.
“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.
The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
AGA CPU: Essentials to prevent complications with ostomies
The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.
Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.
The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.
Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.
Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.
Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.
Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.
Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.
Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.
“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.
This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.
The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.
Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.
The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.
Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.
Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.
Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.
Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.
Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.
Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.
“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.
This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.
The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.
Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.
The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.
Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.
Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.
Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.
Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.
Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.
Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.
“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.
This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA CPU focuses on noninvasive tests in patients with NAFLD
Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.
The update, published online in Gastroenterology, includes eight best practice advice statements.
“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.
“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.
Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.
The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave
elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.
“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.
Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).
Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.
The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”
Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.
Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.
The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.
“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.
Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).
This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.
The update, published online in Gastroenterology, includes eight best practice advice statements.
“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.
“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.
Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.
The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave
elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.
“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.
Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).
Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.
The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”
Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.
Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.
The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.
“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.
Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).
This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.
The update, published online in Gastroenterology, includes eight best practice advice statements.
“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.
“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.
Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.
The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave
elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.
“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.
Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).
Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.
The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”
Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.
Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.
The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.
“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.
Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).
This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
FROM GASTROENTEROLOGY
Crohn’s disease indicators manifest years before diagnosis
Changes in proteins and antibodies suggesting immune dysregulation may be detectable in serum years before clinical manifestation of complicated Crohn’s disease, shows a study recently published in Clinical Gastroenterology and Hepatology.
These preclinical signatures could one day play a role in screening for complicated Crohn’s disease (CD) and in mapping underlying disease pathways, potentially opening doors to new preventive approaches, wrote study authors who were led by Joseph A. Murray, MD, of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“Mounting evidence suggests that the diagnosis of CD is preceded by a lengthy asymptomatic preclinical period,” investigators wrote. “Gaining insight into this phase may allow a better understanding of the primary events that lead to its development and offer potential strategies to predict and prevent the disease including its complications.”
The study, which was a nested case-control study based on the PREDICTS study, included 201 patients with CD who had serum samples archived 2, 4, and 6 years prior to diagnosis, as well as 201 healthy controls who provided serum samples for comparison. Serum samples were analyzed with a comprehensive panel of 1,129 proteomic markers and antimicrobial antibodies.
At time of diagnosis, 47 of the patients with CD (24%) had a complicated phenotype, including stricturing behavior, penetrating behavior, or need for early surgery.
“The unique availability of preclinical samples collected at multiple time points allowed us to examine the sequence of immunological changes and protein biomarkers that occurred before diagnosis,” the investigators wrote. “We also evaluated a wide array of protein biomarkers, utilizing a novel proteomic platform, and applied novel rigorous statistical approaches, which allowed us to discover the potential biomarkers and biologic pathways for the complicated phenotypes even before diagnosis.”
As early as 6 years before diagnosis, patients with complicated CD had significantly higher levels of antimicrobial antibodies than patients with noncomplicated CD, as well as elevations in 22 protein biomarkers indicating immune dysregulation.
Specifically, complicated CD was preceded by elevated anti–Saccharomyces cerevisiae antibodies (ASCA) IgA/IgG, anti-Flagellin antibodies, and other proteins linked with fibrosis, adaptive immunity, and innate immunity. Simultaneously, the same patients had reduced levels of protein biomarkers linked with protection against fibrosis and tissue damage. Network analysis added weight to these findings by demonstrating a significant correlation between ASCA IgA/IgG and protein biomarkers tied to innate immunity and lack of factors for tissue protection.
“Altogether, the hypothesis can be proposed that the combination of increasing levels of inflammatory cytokines, loss of anti-inflammatory proteins, and production of antimicrobial antibodies could accelerate and magnify tissue destruction and fibrosis driving complications at diagnosis in CD,” the investigators wrote. “These data support the concept that complicated CD may not always be the result of the progression of an uncontrolled inflammatory disease but may also be the consequence of a unique pathophysiological process.”
The findings deserve further investigation as they could lead to new clinical tools for screening and intervention. “The serological signature that we identified could help to further select subjects at risk of developing complicated CD who could be preferential candidates for preventative strategies,” investigators wrote.
The investigators disclosed relationships with Janssen, AbbVie, Galapagos, and others.
Certainly, insights into the preclinical phase of a disease state such as IBD may allow for potential preventive interventions and possible avoidance of disease-related complications. In this important study by Choung and colleagues, pre-diagnosis serum analyses of protein biomarkers and antimicrobial antibodies revealed that certain signatures are associated with a complicated phenotype of Crohn’s disease at time of diagnosis compared to patients with uncomplicated Crohn’s disease. Specifically, patients with complicated Crohn’s disease at diagnosis had higher levels of anti-microbial antibodies and altered protein biomarkers with overproduction of inflammatory proteins 6 years before their date of diagnosis, likely reflecting a dysregulated innate immune system, excessive adaptive response to microbial antigens, and fibrosis.
Although the results of this study are very exciting and may help support further research to risk stratify and possibly prevent progression of Crohn’s disease in the pre-clinical stage, additional confirmatory studies are needed before these observations are ready for real world application.
Jana G. Al Hashash, MD, MSc, associate professor of medicine, Mayo Clinic, Florida. She has no conflicts.
Certainly, insights into the preclinical phase of a disease state such as IBD may allow for potential preventive interventions and possible avoidance of disease-related complications. In this important study by Choung and colleagues, pre-diagnosis serum analyses of protein biomarkers and antimicrobial antibodies revealed that certain signatures are associated with a complicated phenotype of Crohn’s disease at time of diagnosis compared to patients with uncomplicated Crohn’s disease. Specifically, patients with complicated Crohn’s disease at diagnosis had higher levels of anti-microbial antibodies and altered protein biomarkers with overproduction of inflammatory proteins 6 years before their date of diagnosis, likely reflecting a dysregulated innate immune system, excessive adaptive response to microbial antigens, and fibrosis.
Although the results of this study are very exciting and may help support further research to risk stratify and possibly prevent progression of Crohn’s disease in the pre-clinical stage, additional confirmatory studies are needed before these observations are ready for real world application.
Jana G. Al Hashash, MD, MSc, associate professor of medicine, Mayo Clinic, Florida. She has no conflicts.
Certainly, insights into the preclinical phase of a disease state such as IBD may allow for potential preventive interventions and possible avoidance of disease-related complications. In this important study by Choung and colleagues, pre-diagnosis serum analyses of protein biomarkers and antimicrobial antibodies revealed that certain signatures are associated with a complicated phenotype of Crohn’s disease at time of diagnosis compared to patients with uncomplicated Crohn’s disease. Specifically, patients with complicated Crohn’s disease at diagnosis had higher levels of anti-microbial antibodies and altered protein biomarkers with overproduction of inflammatory proteins 6 years before their date of diagnosis, likely reflecting a dysregulated innate immune system, excessive adaptive response to microbial antigens, and fibrosis.
Although the results of this study are very exciting and may help support further research to risk stratify and possibly prevent progression of Crohn’s disease in the pre-clinical stage, additional confirmatory studies are needed before these observations are ready for real world application.
Jana G. Al Hashash, MD, MSc, associate professor of medicine, Mayo Clinic, Florida. She has no conflicts.
Changes in proteins and antibodies suggesting immune dysregulation may be detectable in serum years before clinical manifestation of complicated Crohn’s disease, shows a study recently published in Clinical Gastroenterology and Hepatology.
These preclinical signatures could one day play a role in screening for complicated Crohn’s disease (CD) and in mapping underlying disease pathways, potentially opening doors to new preventive approaches, wrote study authors who were led by Joseph A. Murray, MD, of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“Mounting evidence suggests that the diagnosis of CD is preceded by a lengthy asymptomatic preclinical period,” investigators wrote. “Gaining insight into this phase may allow a better understanding of the primary events that lead to its development and offer potential strategies to predict and prevent the disease including its complications.”
The study, which was a nested case-control study based on the PREDICTS study, included 201 patients with CD who had serum samples archived 2, 4, and 6 years prior to diagnosis, as well as 201 healthy controls who provided serum samples for comparison. Serum samples were analyzed with a comprehensive panel of 1,129 proteomic markers and antimicrobial antibodies.
At time of diagnosis, 47 of the patients with CD (24%) had a complicated phenotype, including stricturing behavior, penetrating behavior, or need for early surgery.
“The unique availability of preclinical samples collected at multiple time points allowed us to examine the sequence of immunological changes and protein biomarkers that occurred before diagnosis,” the investigators wrote. “We also evaluated a wide array of protein biomarkers, utilizing a novel proteomic platform, and applied novel rigorous statistical approaches, which allowed us to discover the potential biomarkers and biologic pathways for the complicated phenotypes even before diagnosis.”
As early as 6 years before diagnosis, patients with complicated CD had significantly higher levels of antimicrobial antibodies than patients with noncomplicated CD, as well as elevations in 22 protein biomarkers indicating immune dysregulation.
Specifically, complicated CD was preceded by elevated anti–Saccharomyces cerevisiae antibodies (ASCA) IgA/IgG, anti-Flagellin antibodies, and other proteins linked with fibrosis, adaptive immunity, and innate immunity. Simultaneously, the same patients had reduced levels of protein biomarkers linked with protection against fibrosis and tissue damage. Network analysis added weight to these findings by demonstrating a significant correlation between ASCA IgA/IgG and protein biomarkers tied to innate immunity and lack of factors for tissue protection.
“Altogether, the hypothesis can be proposed that the combination of increasing levels of inflammatory cytokines, loss of anti-inflammatory proteins, and production of antimicrobial antibodies could accelerate and magnify tissue destruction and fibrosis driving complications at diagnosis in CD,” the investigators wrote. “These data support the concept that complicated CD may not always be the result of the progression of an uncontrolled inflammatory disease but may also be the consequence of a unique pathophysiological process.”
The findings deserve further investigation as they could lead to new clinical tools for screening and intervention. “The serological signature that we identified could help to further select subjects at risk of developing complicated CD who could be preferential candidates for preventative strategies,” investigators wrote.
The investigators disclosed relationships with Janssen, AbbVie, Galapagos, and others.
Changes in proteins and antibodies suggesting immune dysregulation may be detectable in serum years before clinical manifestation of complicated Crohn’s disease, shows a study recently published in Clinical Gastroenterology and Hepatology.
These preclinical signatures could one day play a role in screening for complicated Crohn’s disease (CD) and in mapping underlying disease pathways, potentially opening doors to new preventive approaches, wrote study authors who were led by Joseph A. Murray, MD, of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“Mounting evidence suggests that the diagnosis of CD is preceded by a lengthy asymptomatic preclinical period,” investigators wrote. “Gaining insight into this phase may allow a better understanding of the primary events that lead to its development and offer potential strategies to predict and prevent the disease including its complications.”
The study, which was a nested case-control study based on the PREDICTS study, included 201 patients with CD who had serum samples archived 2, 4, and 6 years prior to diagnosis, as well as 201 healthy controls who provided serum samples for comparison. Serum samples were analyzed with a comprehensive panel of 1,129 proteomic markers and antimicrobial antibodies.
At time of diagnosis, 47 of the patients with CD (24%) had a complicated phenotype, including stricturing behavior, penetrating behavior, or need for early surgery.
“The unique availability of preclinical samples collected at multiple time points allowed us to examine the sequence of immunological changes and protein biomarkers that occurred before diagnosis,” the investigators wrote. “We also evaluated a wide array of protein biomarkers, utilizing a novel proteomic platform, and applied novel rigorous statistical approaches, which allowed us to discover the potential biomarkers and biologic pathways for the complicated phenotypes even before diagnosis.”
As early as 6 years before diagnosis, patients with complicated CD had significantly higher levels of antimicrobial antibodies than patients with noncomplicated CD, as well as elevations in 22 protein biomarkers indicating immune dysregulation.
Specifically, complicated CD was preceded by elevated anti–Saccharomyces cerevisiae antibodies (ASCA) IgA/IgG, anti-Flagellin antibodies, and other proteins linked with fibrosis, adaptive immunity, and innate immunity. Simultaneously, the same patients had reduced levels of protein biomarkers linked with protection against fibrosis and tissue damage. Network analysis added weight to these findings by demonstrating a significant correlation between ASCA IgA/IgG and protein biomarkers tied to innate immunity and lack of factors for tissue protection.
“Altogether, the hypothesis can be proposed that the combination of increasing levels of inflammatory cytokines, loss of anti-inflammatory proteins, and production of antimicrobial antibodies could accelerate and magnify tissue destruction and fibrosis driving complications at diagnosis in CD,” the investigators wrote. “These data support the concept that complicated CD may not always be the result of the progression of an uncontrolled inflammatory disease but may also be the consequence of a unique pathophysiological process.”
The findings deserve further investigation as they could lead to new clinical tools for screening and intervention. “The serological signature that we identified could help to further select subjects at risk of developing complicated CD who could be preferential candidates for preventative strategies,” investigators wrote.
The investigators disclosed relationships with Janssen, AbbVie, Galapagos, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY