IBD & Intestinal Disorders

Key clinical point: The risk for incident irritable bowel syndrome (IBS) was significantly higher in individuals in the highest vs lowest quartile of nonalcoholic fatty liver index and in those with a diagnosis of nonalcoholic fatty liver disease (NAFLD).

Major finding: The risk of developing IBS was 21% higher among individuals in the highest vs lowest quartile of fatty liver index (hazard ratio [HR] 1.21; P_trend < .001) and 13% higher among patients with vs without NAFLD (HR 1.13; 95% CI 1.05-1.17).

Study details: Findings are from an analysis of 396,838 participants from a large-scale prospective cohort who were free from IBS, any cancer, inflammatory bowel disease, alcoholic liver disease, and celiac disease, of which 38.6% had an NAFLD diagnosis.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Wu S et al. Non-alcoholic fatty liver is associated with increased risk of irritable bowel syndrome: A prospective cohort study. BMC Med. 2022;20(1):262 (Aug 22). Doi: 10.1186/s12916-022-02460-8

Key clinical point: The risk for incident irritable bowel syndrome (IBS) was significantly higher in individuals in the highest vs lowest quartile of nonalcoholic fatty liver index and in those with a diagnosis of nonalcoholic fatty liver disease (NAFLD).

Major finding: The risk of developing IBS was 21% higher among individuals in the highest vs lowest quartile of fatty liver index (hazard ratio [HR] 1.21; P_trend < .001) and 13% higher among patients with vs without NAFLD (HR 1.13; 95% CI 1.05-1.17).

Study details: Findings are from an analysis of 396,838 participants from a large-scale prospective cohort who were free from IBS, any cancer, inflammatory bowel disease, alcoholic liver disease, and celiac disease, of which 38.6% had an NAFLD diagnosis.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Wu S et al. Non-alcoholic fatty liver is associated with increased risk of irritable bowel syndrome: A prospective cohort study. BMC Med. 2022;20(1):262 (Aug 22). Doi: 10.1186/s12916-022-02460-8

Key clinical point: The risk for incident irritable bowel syndrome (IBS) was significantly higher in individuals in the highest vs lowest quartile of nonalcoholic fatty liver index and in those with a diagnosis of nonalcoholic fatty liver disease (NAFLD).

Major finding: The risk of developing IBS was 21% higher among individuals in the highest vs lowest quartile of fatty liver index (hazard ratio [HR] 1.21; P_trend < .001) and 13% higher among patients with vs without NAFLD (HR 1.13; 95% CI 1.05-1.17).

Study details: Findings are from an analysis of 396,838 participants from a large-scale prospective cohort who were free from IBS, any cancer, inflammatory bowel disease, alcoholic liver disease, and celiac disease, of which 38.6% had an NAFLD diagnosis.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Wu S et al. Non-alcoholic fatty liver is associated with increased risk of irritable bowel syndrome: A prospective cohort study. BMC Med. 2022;20(1):262 (Aug 22). Doi: 10.1186/s12916-022-02460-8

Key clinical point: Once-daily 75 mg vibegron was not associated with a clinically significant improvement in irritable bowel syndrome (IBS)-associated abdominal pain in women with diarrhea-predominant IBS (IBS-D) or mixed diarrhea/constipation IBS (IBS-M).

Major finding: At week 12, the percentage of women with IBS-D (40.9% vs 42.9%; P = .8222) or IBS-M (28.9% vs 24.4%; P = .6151) experiencing ≥30% improvement in IBS-associated abdominal pain was not significantly different with vibegron vs placebo. The incidence of treatment-emergent adverse events was comparable between the treatment groups.

Study details: The data come from a phase 2 randomized controlled trial including 222 adult women with IBS-D or IBS-M who were randomly assigned to receive 75 mg vibegron (n = 111) or placebo (n = 111).

Disclosures: This study was funded by Urovant Sciences. J King, D Shortino, C Schaumburg, and C Haag-Molkenteller declared being former employees of Urovant Sciences. Some authors declared receiving research grants or serving as consultants or on scientific advisory boards for various sources, including Urovant Sciences.

Source: Lacy BE et al. Efficacy and safety of vibegron for the treatment of irritable bowel syndrome in women: Results of a randomized, double-blind, placebo-controlled phase 2 trial. Neurogastroenterol Motil. 2022;e14448 (Aug 16). Doi: 10.1111/nmo.14448

Key clinical point: Once-daily 75 mg vibegron was not associated with a clinically significant improvement in irritable bowel syndrome (IBS)-associated abdominal pain in women with diarrhea-predominant IBS (IBS-D) or mixed diarrhea/constipation IBS (IBS-M).

Major finding: At week 12, the percentage of women with IBS-D (40.9% vs 42.9%; P = .8222) or IBS-M (28.9% vs 24.4%; P = .6151) experiencing ≥30% improvement in IBS-associated abdominal pain was not significantly different with vibegron vs placebo. The incidence of treatment-emergent adverse events was comparable between the treatment groups.

Study details: The data come from a phase 2 randomized controlled trial including 222 adult women with IBS-D or IBS-M who were randomly assigned to receive 75 mg vibegron (n = 111) or placebo (n = 111).

Disclosures: This study was funded by Urovant Sciences. J King, D Shortino, C Schaumburg, and C Haag-Molkenteller declared being former employees of Urovant Sciences. Some authors declared receiving research grants or serving as consultants or on scientific advisory boards for various sources, including Urovant Sciences.

Source: Lacy BE et al. Efficacy and safety of vibegron for the treatment of irritable bowel syndrome in women: Results of a randomized, double-blind, placebo-controlled phase 2 trial. Neurogastroenterol Motil. 2022;e14448 (Aug 16). Doi: 10.1111/nmo.14448

Key clinical point: Once-daily 75 mg vibegron was not associated with a clinically significant improvement in irritable bowel syndrome (IBS)-associated abdominal pain in women with diarrhea-predominant IBS (IBS-D) or mixed diarrhea/constipation IBS (IBS-M).

Major finding: At week 12, the percentage of women with IBS-D (40.9% vs 42.9%; P = .8222) or IBS-M (28.9% vs 24.4%; P = .6151) experiencing ≥30% improvement in IBS-associated abdominal pain was not significantly different with vibegron vs placebo. The incidence of treatment-emergent adverse events was comparable between the treatment groups.

Study details: The data come from a phase 2 randomized controlled trial including 222 adult women with IBS-D or IBS-M who were randomly assigned to receive 75 mg vibegron (n = 111) or placebo (n = 111).

Disclosures: This study was funded by Urovant Sciences. J King, D Shortino, C Schaumburg, and C Haag-Molkenteller declared being former employees of Urovant Sciences. Some authors declared receiving research grants or serving as consultants or on scientific advisory boards for various sources, including Urovant Sciences.

Source: Lacy BE et al. Efficacy and safety of vibegron for the treatment of irritable bowel syndrome in women: Results of a randomized, double-blind, placebo-controlled phase 2 trial. Neurogastroenterol Motil. 2022;e14448 (Aug 16). Doi: 10.1111/nmo.14448

Key clinical point: An 8-week treatment with mesalazine offered no clear benefits over placebo for global improvement of irritable bowel syndrome (IBS) symptoms.

Major finding: A similar proportion of patients receiving mesalazine vs placebo reported satisfactory relief of IBS symptoms during ≥50% of the treatment weeks (36% vs 30%; P = .40); however, the improvement in abdominal bloating was significantly greater in the mesalazine vs placebo group (P = .02).

Study details: The data come from a randomized controlled trial including 181 patients with IBS who were assigned to an 8-week treatment with 2400 mg mesalazine orally or placebo once daily.

Disclosures: This study was funded by Eurostars project grant from Tillotts Pharma AB and by the Swedish state. Some authors declared receiving research grants or serving as consultants or on advisory boards for various sources, including Tillotts Pharma.

Source: Tejera VC et al. Randomised clinical trial and meta-analysis: Mesalazine treatment in irritable bowel syndrome—Effects on gastrointestinal symptoms and rectal biomarkers of immune activity. Aliment Pharmacol Ther. 2022;56(6):968-979 (Aug 8). Doi: 10.1111/apt.17182

Key clinical point: An 8-week treatment with mesalazine offered no clear benefits over placebo for global improvement of irritable bowel syndrome (IBS) symptoms.

Major finding: A similar proportion of patients receiving mesalazine vs placebo reported satisfactory relief of IBS symptoms during ≥50% of the treatment weeks (36% vs 30%; P = .40); however, the improvement in abdominal bloating was significantly greater in the mesalazine vs placebo group (P = .02).

Study details: The data come from a randomized controlled trial including 181 patients with IBS who were assigned to an 8-week treatment with 2400 mg mesalazine orally or placebo once daily.

Disclosures: This study was funded by Eurostars project grant from Tillotts Pharma AB and by the Swedish state. Some authors declared receiving research grants or serving as consultants or on advisory boards for various sources, including Tillotts Pharma.

Source: Tejera VC et al. Randomised clinical trial and meta-analysis: Mesalazine treatment in irritable bowel syndrome—Effects on gastrointestinal symptoms and rectal biomarkers of immune activity. Aliment Pharmacol Ther. 2022;56(6):968-979 (Aug 8). Doi: 10.1111/apt.17182

Key clinical point: An 8-week treatment with mesalazine offered no clear benefits over placebo for global improvement of irritable bowel syndrome (IBS) symptoms.

Major finding: A similar proportion of patients receiving mesalazine vs placebo reported satisfactory relief of IBS symptoms during ≥50% of the treatment weeks (36% vs 30%; P = .40); however, the improvement in abdominal bloating was significantly greater in the mesalazine vs placebo group (P = .02).

Study details: The data come from a randomized controlled trial including 181 patients with IBS who were assigned to an 8-week treatment with 2400 mg mesalazine orally or placebo once daily.

Disclosures: This study was funded by Eurostars project grant from Tillotts Pharma AB and by the Swedish state. Some authors declared receiving research grants or serving as consultants or on advisory boards for various sources, including Tillotts Pharma.

Source: Tejera VC et al. Randomised clinical trial and meta-analysis: Mesalazine treatment in irritable bowel syndrome—Effects on gastrointestinal symptoms and rectal biomarkers of immune activity. Aliment Pharmacol Ther. 2022;56(6):968-979 (Aug 8). Doi: 10.1111/apt.17182

Patients with inflammatory bowel disease (IBD) taking ustekinumab (Stelara) are less likely to have infections as a side effect than those taking tofacitinib (Xeljanz) or anti–tumor necrosis factor-alpha (anti-TNF), researchers say.

Although the risk of infections is not large for any of these drugs, clinicians should nonetheless take it into account, given their similar efficacy, said Ashwin Ananthakrishnan, MD, associate professor of medicine at Massachusetts General Hospital, Boston.

“These findings may not dramatically change prescribing patterns, but in those who may be particularly vulnerable for infection, they could point toward the safer biologic being Stelara,” he told this news organization.

The study by Dr. Ananthakrishnan and his colleagues was published in Clinical Gastroenterology and Hepatology.

Biologic and small-molecule immunosuppressive therapies have emerged as effective treatments for Crohn’s disease and ulcerative colitis, the two conditions that comprise IBD.

But the recent proliferation of drugs in these classes with different mechanisms of action has made prescribing decisions complicated. And because the drugs suppress the immune system, they can make patients vulnerable to infection.

Randomized controlled trials, even those comparing the drugs head to head, have not been large enough to compare safety outcomes with statistical accuracy, Dr. Ananthakrishnan and his colleagues found.
 

Accessing a large, real-world cohort

To help fill this gap, they analyzed data on 89,972,617 people enrolled in Aetna, the nationwide U.S. health insurance plan, from 2008-2019.

They identified 19,096 patients whose IBD was treated with anti-TNF agents, 2,420 with ustekinumab, and 305 with tofacitinib. The number of patients taking tofacitinib is small because it is a newer drug, Dr. Ananthakrishnan said.

They found a higher rate of infection and rate of infection-related hospitalization for the patients taking anti-TNF agents (44% and 7%, respectively), compared with those taking ustekinumab (32% and 4%, respectively) over the course of up to a year.

The researchers adjusted for age, sex, IBD duration, prior corticosteroid use, prior immunomodulator use, prior IBD hospitalization, and comorbidities, after which they then compared the risks of infection.

They found that patients taking ustekinumab were 7% less likely to have any infection than patients taking anti-TNF agents (hazard ratio, 0.93), a statistically significant difference (95% confidence interval, 0.86-0.99; P = .041). The reduction in the risk of infection-related hospitalizations was similar but not statistically significant.

The advantage with ustekinumab over anti-TNF agents was larger for patients with comorbidities. There was a 25% reduction in the risk of infections for patients taking ustekinumab who had a Charlson comorbidity index score of at least 2 and who were younger than 65 years (HRm 0.71; 95% CI, 0.58-0.87; P < .001).

For patients taking tofacitinib, there were no significant differences in the rate of infection (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05), compared with TNF-antagonists.

The respiratory system and the urinary tract were the most common sites of infections. Bacterial, viral, and fungal infections were similarly distributed in the three groups.
 

Remaining questions

Further research is needed, said Dr. Ananthakrishnan, as “to understand the comparative safety may be particularly important for vulnerable populations, like those who are older or have other underlying comorbidity, where safety is increasingly an important issue.”

The findings are similar to those of other studies comparing infections in association with ustekinumab to anti-TNF medications for related conditions, such as psoriatic arthritis and psoriasis, he said.

Clinicians have seen similar differences among the drugs in clinical practice, said Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at Cleveland Clinic, Ohio, who was not involved in the study.

“It aligns well with what we’ve thought, but it’s nice to see in a publication,” he said in an interview.

The implications of the study are limited, because it was not a prospective randomized trial and because the number of patients taking tofacitinib was so small, Dr. Regueiro added.

Another limitation is that the patients who were admitted to the hospital in this database were not necessarily admitted because of their infections, said Stephen Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who also was not involved in the study.

Dr. Hanauer told this news organization that comparisons with other agents would be helpful.

“They didn’t look at vedolizumab (Entyvio) in this database,” he said. “Entyvio is generally considered to be safer than TNF inhibitors or tofacitinib with fairly comparable safety to ustekinumab.”

Dr. Ananthakrishnan reported financial relationships with Gilead, Ikena Therapeutics, and Sun Pharma. Dr. Regueiro reported financial relationships with AbbVie, BMS, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead, UCB, Miraca Labs, Amgen, Celgene, Seres, Allergan, Salix, Prometheus, Lilly, TARGET Pharma Solutions, Alfasigigma, and BMS. Dr. Hanauer reported financial relationships with Janssen Pharmaceuticals, AbbVie, Takeda Pharmaceutical, and Pfizer.

A version of this article first appeared on Medscape.com.

Patients with inflammatory bowel disease (IBD) taking ustekinumab (Stelara) are less likely to have infections as a side effect than those taking tofacitinib (Xeljanz) or anti–tumor necrosis factor-alpha (anti-TNF), researchers say.

Although the risk of infections is not large for any of these drugs, clinicians should nonetheless take it into account, given their similar efficacy, said Ashwin Ananthakrishnan, MD, associate professor of medicine at Massachusetts General Hospital, Boston.

“These findings may not dramatically change prescribing patterns, but in those who may be particularly vulnerable for infection, they could point toward the safer biologic being Stelara,” he told this news organization.

The study by Dr. Ananthakrishnan and his colleagues was published in Clinical Gastroenterology and Hepatology.

Biologic and small-molecule immunosuppressive therapies have emerged as effective treatments for Crohn’s disease and ulcerative colitis, the two conditions that comprise IBD.

But the recent proliferation of drugs in these classes with different mechanisms of action has made prescribing decisions complicated. And because the drugs suppress the immune system, they can make patients vulnerable to infection.

Randomized controlled trials, even those comparing the drugs head to head, have not been large enough to compare safety outcomes with statistical accuracy, Dr. Ananthakrishnan and his colleagues found.
 

Accessing a large, real-world cohort

To help fill this gap, they analyzed data on 89,972,617 people enrolled in Aetna, the nationwide U.S. health insurance plan, from 2008-2019.

They identified 19,096 patients whose IBD was treated with anti-TNF agents, 2,420 with ustekinumab, and 305 with tofacitinib. The number of patients taking tofacitinib is small because it is a newer drug, Dr. Ananthakrishnan said.

They found a higher rate of infection and rate of infection-related hospitalization for the patients taking anti-TNF agents (44% and 7%, respectively), compared with those taking ustekinumab (32% and 4%, respectively) over the course of up to a year.

The researchers adjusted for age, sex, IBD duration, prior corticosteroid use, prior immunomodulator use, prior IBD hospitalization, and comorbidities, after which they then compared the risks of infection.

They found that patients taking ustekinumab were 7% less likely to have any infection than patients taking anti-TNF agents (hazard ratio, 0.93), a statistically significant difference (95% confidence interval, 0.86-0.99; P = .041). The reduction in the risk of infection-related hospitalizations was similar but not statistically significant.

The advantage with ustekinumab over anti-TNF agents was larger for patients with comorbidities. There was a 25% reduction in the risk of infections for patients taking ustekinumab who had a Charlson comorbidity index score of at least 2 and who were younger than 65 years (HRm 0.71; 95% CI, 0.58-0.87; P < .001).

For patients taking tofacitinib, there were no significant differences in the rate of infection (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05), compared with TNF-antagonists.

The respiratory system and the urinary tract were the most common sites of infections. Bacterial, viral, and fungal infections were similarly distributed in the three groups.
 

Remaining questions

Further research is needed, said Dr. Ananthakrishnan, as “to understand the comparative safety may be particularly important for vulnerable populations, like those who are older or have other underlying comorbidity, where safety is increasingly an important issue.”

The findings are similar to those of other studies comparing infections in association with ustekinumab to anti-TNF medications for related conditions, such as psoriatic arthritis and psoriasis, he said.

Clinicians have seen similar differences among the drugs in clinical practice, said Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at Cleveland Clinic, Ohio, who was not involved in the study.

“It aligns well with what we’ve thought, but it’s nice to see in a publication,” he said in an interview.

The implications of the study are limited, because it was not a prospective randomized trial and because the number of patients taking tofacitinib was so small, Dr. Regueiro added.

Another limitation is that the patients who were admitted to the hospital in this database were not necessarily admitted because of their infections, said Stephen Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who also was not involved in the study.

Dr. Hanauer told this news organization that comparisons with other agents would be helpful.

“They didn’t look at vedolizumab (Entyvio) in this database,” he said. “Entyvio is generally considered to be safer than TNF inhibitors or tofacitinib with fairly comparable safety to ustekinumab.”

Dr. Ananthakrishnan reported financial relationships with Gilead, Ikena Therapeutics, and Sun Pharma. Dr. Regueiro reported financial relationships with AbbVie, BMS, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead, UCB, Miraca Labs, Amgen, Celgene, Seres, Allergan, Salix, Prometheus, Lilly, TARGET Pharma Solutions, Alfasigigma, and BMS. Dr. Hanauer reported financial relationships with Janssen Pharmaceuticals, AbbVie, Takeda Pharmaceutical, and Pfizer.

A version of this article first appeared on Medscape.com.

Patients with inflammatory bowel disease (IBD) taking ustekinumab (Stelara) are less likely to have infections as a side effect than those taking tofacitinib (Xeljanz) or anti–tumor necrosis factor-alpha (anti-TNF), researchers say.

Although the risk of infections is not large for any of these drugs, clinicians should nonetheless take it into account, given their similar efficacy, said Ashwin Ananthakrishnan, MD, associate professor of medicine at Massachusetts General Hospital, Boston.

“These findings may not dramatically change prescribing patterns, but in those who may be particularly vulnerable for infection, they could point toward the safer biologic being Stelara,” he told this news organization.

The study by Dr. Ananthakrishnan and his colleagues was published in Clinical Gastroenterology and Hepatology.

Biologic and small-molecule immunosuppressive therapies have emerged as effective treatments for Crohn’s disease and ulcerative colitis, the two conditions that comprise IBD.

But the recent proliferation of drugs in these classes with different mechanisms of action has made prescribing decisions complicated. And because the drugs suppress the immune system, they can make patients vulnerable to infection.

Randomized controlled trials, even those comparing the drugs head to head, have not been large enough to compare safety outcomes with statistical accuracy, Dr. Ananthakrishnan and his colleagues found.
 

Accessing a large, real-world cohort

To help fill this gap, they analyzed data on 89,972,617 people enrolled in Aetna, the nationwide U.S. health insurance plan, from 2008-2019.

They identified 19,096 patients whose IBD was treated with anti-TNF agents, 2,420 with ustekinumab, and 305 with tofacitinib. The number of patients taking tofacitinib is small because it is a newer drug, Dr. Ananthakrishnan said.

They found a higher rate of infection and rate of infection-related hospitalization for the patients taking anti-TNF agents (44% and 7%, respectively), compared with those taking ustekinumab (32% and 4%, respectively) over the course of up to a year.

The researchers adjusted for age, sex, IBD duration, prior corticosteroid use, prior immunomodulator use, prior IBD hospitalization, and comorbidities, after which they then compared the risks of infection.

They found that patients taking ustekinumab were 7% less likely to have any infection than patients taking anti-TNF agents (hazard ratio, 0.93), a statistically significant difference (95% confidence interval, 0.86-0.99; P = .041). The reduction in the risk of infection-related hospitalizations was similar but not statistically significant.

The advantage with ustekinumab over anti-TNF agents was larger for patients with comorbidities. There was a 25% reduction in the risk of infections for patients taking ustekinumab who had a Charlson comorbidity index score of at least 2 and who were younger than 65 years (HRm 0.71; 95% CI, 0.58-0.87; P < .001).

For patients taking tofacitinib, there were no significant differences in the rate of infection (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05), compared with TNF-antagonists.

The respiratory system and the urinary tract were the most common sites of infections. Bacterial, viral, and fungal infections were similarly distributed in the three groups.
 

Remaining questions

Further research is needed, said Dr. Ananthakrishnan, as “to understand the comparative safety may be particularly important for vulnerable populations, like those who are older or have other underlying comorbidity, where safety is increasingly an important issue.”

The findings are similar to those of other studies comparing infections in association with ustekinumab to anti-TNF medications for related conditions, such as psoriatic arthritis and psoriasis, he said.

Clinicians have seen similar differences among the drugs in clinical practice, said Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at Cleveland Clinic, Ohio, who was not involved in the study.

“It aligns well with what we’ve thought, but it’s nice to see in a publication,” he said in an interview.

The implications of the study are limited, because it was not a prospective randomized trial and because the number of patients taking tofacitinib was so small, Dr. Regueiro added.

Another limitation is that the patients who were admitted to the hospital in this database were not necessarily admitted because of their infections, said Stephen Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who also was not involved in the study.

Dr. Hanauer told this news organization that comparisons with other agents would be helpful.

“They didn’t look at vedolizumab (Entyvio) in this database,” he said. “Entyvio is generally considered to be safer than TNF inhibitors or tofacitinib with fairly comparable safety to ustekinumab.”

Dr. Ananthakrishnan reported financial relationships with Gilead, Ikena Therapeutics, and Sun Pharma. Dr. Regueiro reported financial relationships with AbbVie, BMS, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead, UCB, Miraca Labs, Amgen, Celgene, Seres, Allergan, Salix, Prometheus, Lilly, TARGET Pharma Solutions, Alfasigigma, and BMS. Dr. Hanauer reported financial relationships with Janssen Pharmaceuticals, AbbVie, Takeda Pharmaceutical, and Pfizer.

A version of this article first appeared on Medscape.com.

Levels of calprotectin, a biomarker used to detect intestinal inflammation, may vary in fecal samples based on an individual’s microbiome composition, according to researchers. The results, if confirmed, might help refine its use in monitoring inflammatory bowel disease (IBD).

Researchers used a new ex vivo functional assay to identify specific bacteria that degrade calprotectin and may play a role in variations found in vivo. “Microbiome-based calibration could improve sensitivity and specificity of fecal calprotectin readouts, thereby facilitating more reliable real-time monitoring and ultimately enabling more timely interventions,” the authors wrote in their research letter, which was published in Gastro Hep Advances.

The standard for diagnosing ulcerative colitis (UC) and Crohn’s disease (CD) is endoscopy and biopsy because it allows both visual and histological examination of the severity and extent of intestinal inflammation, but this cannot be used to monitor patients on an ongoing basis.

Calprotectin is a promising biomarker for intestinal inflammation, but a meta-analysis found that it has a pooled sensitivity of 85% and a pooled specificity of 75% for the diagnosis of endoscopically active inflammatory bowel disease.

The researchers investigated whether an individual’s microbiome can metabolize calprotectin, which would complicate measurement of fecal calprotectin. They recruited 22 individuals with IBD (64% female, 73% with colonic disease), who provided stool samples. They completed a symptom questionnaire in advance of a colonoscopy. Overall, 64% had endoscopically inactive disease, and 82% had clinically inactive disease.

At a cutoff of 50 mcg/g, 9 patients had normal fecal calprotectin levels, and 13 had elevated levels. Those with clinically or endoscopically active disease had higher levels of fecal calprotectin (P < .0001).

There was a significant but poor correlation between disease activity measures and fecal calprotectin levels in CD (r = 0.62; P = .008), but there was no statistically significant association for UC (r = –0.29; P = .6). Endoscopic disease activity was also significantly correlated with fecal calprotectin in CD (r = 0.83; P < .001), but not UC (r = 0.50; P = .4).

The researchers created an ex vivo functional assay to measure calprotectin metabolism by the microbiome. They anaerobically cultured fecal samples in the presence of calprotectin and measured levels of calprotectin after 24 hours. Control samples were grown without microbes, without calprotectin, or lacking both. The researchers tested samples in both standard media and in media with low levels of amino acids, reasoning that the latter condition might encourage catabolism of calprotectin. The cultures with low amino acid content had lower calprotectin levels than those with normal amino acid content (P < .0007).

The researchers found greater calprotectin degradation in the low amino acid media, and the difference was more pronounced among samples taken from individuals with UC than CD (P < .02).

They used metagenomic sequencing data from fecal samples to identify bacterial species associated with calprotectin metabolism. Similarly to previous reports, the researchers found that Firmicutes was dominant, while Subdoligranulum correlated with calprotectin degradation in low amino acid media (P = .04).

For 5 days, they cultured Subdoligranulum variabile in low amino acid media that also contained calprotectin. Calprotectin levels were lower than a control sample with cultured Akkermansia muciniphila, which was previously shown to not be associated with calprotectin degradation in low amino acid media (P = .03). Because Subdoligranulum species were not detectable in 5 of 22 fecal samples, the authors say they are unlikely to be the only species capable of metabolizing calprotectin.

Among IBD patients, only one had both endoscopically active colitis and a low fecal calprotectin level. The patient’s micobiome had Subdoligranulum present, and their fecal sample was able to metabolize calprotectin in the functional assay.

The study was limited by its small sample size, which prevented development of a calibration model for fecal calprotectin, and the researchers called for additional studies among individuals with active colitis.

Levels of calprotectin, a biomarker used to detect intestinal inflammation, may vary in fecal samples based on an individual’s microbiome composition, according to researchers. The results, if confirmed, might help refine its use in monitoring inflammatory bowel disease (IBD).

Researchers used a new ex vivo functional assay to identify specific bacteria that degrade calprotectin and may play a role in variations found in vivo. “Microbiome-based calibration could improve sensitivity and specificity of fecal calprotectin readouts, thereby facilitating more reliable real-time monitoring and ultimately enabling more timely interventions,” the authors wrote in their research letter, which was published in Gastro Hep Advances.

The standard for diagnosing ulcerative colitis (UC) and Crohn’s disease (CD) is endoscopy and biopsy because it allows both visual and histological examination of the severity and extent of intestinal inflammation, but this cannot be used to monitor patients on an ongoing basis.

Calprotectin is a promising biomarker for intestinal inflammation, but a meta-analysis found that it has a pooled sensitivity of 85% and a pooled specificity of 75% for the diagnosis of endoscopically active inflammatory bowel disease.

The researchers investigated whether an individual’s microbiome can metabolize calprotectin, which would complicate measurement of fecal calprotectin. They recruited 22 individuals with IBD (64% female, 73% with colonic disease), who provided stool samples. They completed a symptom questionnaire in advance of a colonoscopy. Overall, 64% had endoscopically inactive disease, and 82% had clinically inactive disease.

At a cutoff of 50 mcg/g, 9 patients had normal fecal calprotectin levels, and 13 had elevated levels. Those with clinically or endoscopically active disease had higher levels of fecal calprotectin (P < .0001).

There was a significant but poor correlation between disease activity measures and fecal calprotectin levels in CD (r = 0.62; P = .008), but there was no statistically significant association for UC (r = –0.29; P = .6). Endoscopic disease activity was also significantly correlated with fecal calprotectin in CD (r = 0.83; P < .001), but not UC (r = 0.50; P = .4).

The researchers created an ex vivo functional assay to measure calprotectin metabolism by the microbiome. They anaerobically cultured fecal samples in the presence of calprotectin and measured levels of calprotectin after 24 hours. Control samples were grown without microbes, without calprotectin, or lacking both. The researchers tested samples in both standard media and in media with low levels of amino acids, reasoning that the latter condition might encourage catabolism of calprotectin. The cultures with low amino acid content had lower calprotectin levels than those with normal amino acid content (P < .0007).

The researchers found greater calprotectin degradation in the low amino acid media, and the difference was more pronounced among samples taken from individuals with UC than CD (P < .02).

They used metagenomic sequencing data from fecal samples to identify bacterial species associated with calprotectin metabolism. Similarly to previous reports, the researchers found that Firmicutes was dominant, while Subdoligranulum correlated with calprotectin degradation in low amino acid media (P = .04).

For 5 days, they cultured Subdoligranulum variabile in low amino acid media that also contained calprotectin. Calprotectin levels were lower than a control sample with cultured Akkermansia muciniphila, which was previously shown to not be associated with calprotectin degradation in low amino acid media (P = .03). Because Subdoligranulum species were not detectable in 5 of 22 fecal samples, the authors say they are unlikely to be the only species capable of metabolizing calprotectin.

Among IBD patients, only one had both endoscopically active colitis and a low fecal calprotectin level. The patient’s micobiome had Subdoligranulum present, and their fecal sample was able to metabolize calprotectin in the functional assay.

The study was limited by its small sample size, which prevented development of a calibration model for fecal calprotectin, and the researchers called for additional studies among individuals with active colitis.

Levels of calprotectin, a biomarker used to detect intestinal inflammation, may vary in fecal samples based on an individual’s microbiome composition, according to researchers. The results, if confirmed, might help refine its use in monitoring inflammatory bowel disease (IBD).

Researchers used a new ex vivo functional assay to identify specific bacteria that degrade calprotectin and may play a role in variations found in vivo. “Microbiome-based calibration could improve sensitivity and specificity of fecal calprotectin readouts, thereby facilitating more reliable real-time monitoring and ultimately enabling more timely interventions,” the authors wrote in their research letter, which was published in Gastro Hep Advances.

The standard for diagnosing ulcerative colitis (UC) and Crohn’s disease (CD) is endoscopy and biopsy because it allows both visual and histological examination of the severity and extent of intestinal inflammation, but this cannot be used to monitor patients on an ongoing basis.

Calprotectin is a promising biomarker for intestinal inflammation, but a meta-analysis found that it has a pooled sensitivity of 85% and a pooled specificity of 75% for the diagnosis of endoscopically active inflammatory bowel disease.

The researchers investigated whether an individual’s microbiome can metabolize calprotectin, which would complicate measurement of fecal calprotectin. They recruited 22 individuals with IBD (64% female, 73% with colonic disease), who provided stool samples. They completed a symptom questionnaire in advance of a colonoscopy. Overall, 64% had endoscopically inactive disease, and 82% had clinically inactive disease.

At a cutoff of 50 mcg/g, 9 patients had normal fecal calprotectin levels, and 13 had elevated levels. Those with clinically or endoscopically active disease had higher levels of fecal calprotectin (P < .0001).

There was a significant but poor correlation between disease activity measures and fecal calprotectin levels in CD (r = 0.62; P = .008), but there was no statistically significant association for UC (r = –0.29; P = .6). Endoscopic disease activity was also significantly correlated with fecal calprotectin in CD (r = 0.83; P < .001), but not UC (r = 0.50; P = .4).

The researchers created an ex vivo functional assay to measure calprotectin metabolism by the microbiome. They anaerobically cultured fecal samples in the presence of calprotectin and measured levels of calprotectin after 24 hours. Control samples were grown without microbes, without calprotectin, or lacking both. The researchers tested samples in both standard media and in media with low levels of amino acids, reasoning that the latter condition might encourage catabolism of calprotectin. The cultures with low amino acid content had lower calprotectin levels than those with normal amino acid content (P < .0007).

The researchers found greater calprotectin degradation in the low amino acid media, and the difference was more pronounced among samples taken from individuals with UC than CD (P < .02).

They used metagenomic sequencing data from fecal samples to identify bacterial species associated with calprotectin metabolism. Similarly to previous reports, the researchers found that Firmicutes was dominant, while Subdoligranulum correlated with calprotectin degradation in low amino acid media (P = .04).

For 5 days, they cultured Subdoligranulum variabile in low amino acid media that also contained calprotectin. Calprotectin levels were lower than a control sample with cultured Akkermansia muciniphila, which was previously shown to not be associated with calprotectin degradation in low amino acid media (P = .03). Because Subdoligranulum species were not detectable in 5 of 22 fecal samples, the authors say they are unlikely to be the only species capable of metabolizing calprotectin.

Among IBD patients, only one had both endoscopically active colitis and a low fecal calprotectin level. The patient’s micobiome had Subdoligranulum present, and their fecal sample was able to metabolize calprotectin in the functional assay.

The study was limited by its small sample size, which prevented development of a calibration model for fecal calprotectin, and the researchers called for additional studies among individuals with active colitis.

A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.

Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.

“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.

“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.

The study was published online in the American Journal of Gastroenterology.
 

Taking a second look

Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.

To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.

First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.

However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).

The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.

The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.

While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.

They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
 

Good study, reassuring data

“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”

Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.

“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.

“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.

NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.

In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”

Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.

“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.

The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.

Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.

“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.

“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.

The study was published online in the American Journal of Gastroenterology.
 

Taking a second look

Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.

To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.

First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.

However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).

The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.

The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.

While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.

They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
 

Good study, reassuring data

“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”

Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.

“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.

“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.

NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.

In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”

Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.

“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.

The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.

Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.

“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.

“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.

The study was published online in the American Journal of Gastroenterology.
 

Taking a second look

Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.

To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.

First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.

However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).

The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.

The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.

While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.

They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
 

Good study, reassuring data

“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”

Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.

“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.

“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.

NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.

In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”

Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.

“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.

The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.

Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.

“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.

However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.

The study was published online in Nature Genetics.

Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.

To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.

Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.

They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.

Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”

“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.

The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.

The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.

The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.

“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.

Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.

A version of this article first appeared on Medscape.com.

Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.

Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.

“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.

However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.

The study was published online in Nature Genetics.

Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.

To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.

Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.

They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.

Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”

“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.

The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.

The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.

The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.

“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.

Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.

A version of this article first appeared on Medscape.com.

Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.

Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.

“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.

However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.

The study was published online in Nature Genetics.

Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.

To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.

Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.

They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.

Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”

“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.

The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.

The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.

The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.

“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.

Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.

A version of this article first appeared on Medscape.com.

Intestinal ultrasound (IUS) findings correlate strongly with endoscopy results in patients with ulcerative colitis (UC), with treatment responses detected as soon as 8 weeks after starting tofacitinib, a longitudinal prospective study has found.

IUS accurately detected improvements and remission across a variety of scoring methodologies, suggesting that it may be a cost-effective, noninvasive alternative to endoscopic monitoring, reported lead author Floris de Voogd, MD, of Amsterdam University Medical Centers, and colleagues.

“Endoscopy is generally considered as the gold standard for the diagnosis and follow-up of patients with UC,” the investigators wrote in Gastroenterology. “However, endoscopy is an invasive and costly modality and therefore less attractive to perform frequently during the disease course.”

Whereas noninvasive fecal biomarkers are a more economical method of monitoring inflammation and treatment responses, they fail to characterize disease extent and fall short in detecting early endoscopic responses, the investigators added.

The present study aimed to determine if IUS could offer more clinical insight by measuring bowel wall thickness. Thirty patients were enrolled with moderate to severe UC, all with an endoscopic Mayo score of at least 2. Twenty-seven of these patients were evaluable through follow-up, having undergone both IUS and endoscopy at baseline and 8 weeks after starting tofacitinib.

At both time points, IUS findings correlated significantly with endoscopic Mayo score (EMS), UC endoscopic index for severity, and Robarts Histopathology Index, with correlation coefficients of 0.68, 0.73, and 0.49, respectively. Remission according to EMS was defined as a score of 0, and improvement was defined as a score of 1 or less.

Patients with EMS improvement showed lower median bowel wall thickness in the sigmoid colon after 8 weeks of treatment than did patients without improvement (1.8 mm vs. 4.5 mm; P < .0001); patients who were in EMS remission after 8 weeks also had lower median bowel wall thickness of the sigmoid colon (1.4 mm vs. 4.0 mm; P = .016).

The investigators also sought to define cutoff values for bowel wall thickness. The most accurate cutoff values for identifying endoscopic remission and improvement were 2.8 mm (area under the receiver operating curve, 0.87; 95% confidence interval, 0.74-1.00; P = .006) and 3.9 mm (AUROC, 0.92; 95% CI, 0.82-1.00; P < .0001), respectively. Treatment response was best identified by a 32% threshold reduction in thickness (AUROC, 0.87; 95% CI, 0.74-1.00; P = .002).

“Intestinal ultrasound, with bowel wall thickness as the single most important parameter is accurate to determine treatment response to tofacitinib in patients with moderate-severe UC when compared against endoscopy,” the investigators concluded.

Michael Dolinger, MD, MBA, assistant professor of pediatrics and the associate pediatric gastroenterology fellowship program director at the Icahn School of Medicine at Mount Sinai, New York, said the study is noteworthy because it is the first of its kind to show that IUS can accurately monitor treatment responses in UC.

“This study is what we’re looking for now, and in the future,” Dr. Dolinger said in an interview. “We’re looking for noninvasive biomarkers to predict early responses so that we know as clinicians ... if our medicines are working or if we need to pivot and switch effectively.”

For patients, this can mean feeling better quicker while reducing burden of care, he added.

“We can use this study to predict patient responses without having to potentially rescope them in 8 weeks using a 5-minute point-of-care test in the clinic,” Dr. Dolinger said. “It’s huge to be able to say that for patients with colitis, and to provide reassurance that not only are they potentially feeling better, but the medicine is working to change and heal their bowel wall really quickly as well.”

Dr. Dolinger speaks from clinical experience. Over the past 2 years, he and his colleagues at Mount Sinai have been implementing IUS for patients with both UC and Crohn’s disease.

“It’s become part of our standard of care,” Dr. Dolinger said. “This is now emerging in the United States and will soon take hold. There is a lot of interest.”

Dr. Dolinger is one of just a few American physicians credentialed by the International Bowel Ultrasound Group, an organization based out of Europe, Israel, and Canada. Formalized training and certification are necessary, Dr. Dolinger noted, to ensure that this new clinical approach maintains consistency as it is rolled out across the United States.

“We have the unique opportunity to do something from the ground up quickly, but also correctly, meaning that we can train everyone to speak the same language and do the same standardized exams so that all the findings and research are relatable,” Dr. Dolinger said.

He advised interested physicians to contact their local inflammatory bowel disease center to find out if training is available, and if it is, devoting “a lot of time” to the learning process.

“If you’re going to use this potentially as a clinical decision-making tool without using other invasive procedures, you really want to make sure what you’re doing is accurate and correct,” Dr. Dolinger said.

The investigators disclosed relationships with AbbVie, Merck, Takeda, and others. Dr. Dolinger disclosed a relationship with NeuroLogica, a subsidiary of Samsung Electronics.

Intestinal ultrasound (IUS) findings correlate strongly with endoscopy results in patients with ulcerative colitis (UC), with treatment responses detected as soon as 8 weeks after starting tofacitinib, a longitudinal prospective study has found.

IUS accurately detected improvements and remission across a variety of scoring methodologies, suggesting that it may be a cost-effective, noninvasive alternative to endoscopic monitoring, reported lead author Floris de Voogd, MD, of Amsterdam University Medical Centers, and colleagues.

“Endoscopy is generally considered as the gold standard for the diagnosis and follow-up of patients with UC,” the investigators wrote in Gastroenterology. “However, endoscopy is an invasive and costly modality and therefore less attractive to perform frequently during the disease course.”

Whereas noninvasive fecal biomarkers are a more economical method of monitoring inflammation and treatment responses, they fail to characterize disease extent and fall short in detecting early endoscopic responses, the investigators added.

The present study aimed to determine if IUS could offer more clinical insight by measuring bowel wall thickness. Thirty patients were enrolled with moderate to severe UC, all with an endoscopic Mayo score of at least 2. Twenty-seven of these patients were evaluable through follow-up, having undergone both IUS and endoscopy at baseline and 8 weeks after starting tofacitinib.

At both time points, IUS findings correlated significantly with endoscopic Mayo score (EMS), UC endoscopic index for severity, and Robarts Histopathology Index, with correlation coefficients of 0.68, 0.73, and 0.49, respectively. Remission according to EMS was defined as a score of 0, and improvement was defined as a score of 1 or less.

Patients with EMS improvement showed lower median bowel wall thickness in the sigmoid colon after 8 weeks of treatment than did patients without improvement (1.8 mm vs. 4.5 mm; P < .0001); patients who were in EMS remission after 8 weeks also had lower median bowel wall thickness of the sigmoid colon (1.4 mm vs. 4.0 mm; P = .016).

The investigators also sought to define cutoff values for bowel wall thickness. The most accurate cutoff values for identifying endoscopic remission and improvement were 2.8 mm (area under the receiver operating curve, 0.87; 95% confidence interval, 0.74-1.00; P = .006) and 3.9 mm (AUROC, 0.92; 95% CI, 0.82-1.00; P < .0001), respectively. Treatment response was best identified by a 32% threshold reduction in thickness (AUROC, 0.87; 95% CI, 0.74-1.00; P = .002).

“Intestinal ultrasound, with bowel wall thickness as the single most important parameter is accurate to determine treatment response to tofacitinib in patients with moderate-severe UC when compared against endoscopy,” the investigators concluded.

Michael Dolinger, MD, MBA, assistant professor of pediatrics and the associate pediatric gastroenterology fellowship program director at the Icahn School of Medicine at Mount Sinai, New York, said the study is noteworthy because it is the first of its kind to show that IUS can accurately monitor treatment responses in UC.

“This study is what we’re looking for now, and in the future,” Dr. Dolinger said in an interview. “We’re looking for noninvasive biomarkers to predict early responses so that we know as clinicians ... if our medicines are working or if we need to pivot and switch effectively.”

For patients, this can mean feeling better quicker while reducing burden of care, he added.

“We can use this study to predict patient responses without having to potentially rescope them in 8 weeks using a 5-minute point-of-care test in the clinic,” Dr. Dolinger said. “It’s huge to be able to say that for patients with colitis, and to provide reassurance that not only are they potentially feeling better, but the medicine is working to change and heal their bowel wall really quickly as well.”

Dr. Dolinger speaks from clinical experience. Over the past 2 years, he and his colleagues at Mount Sinai have been implementing IUS for patients with both UC and Crohn’s disease.

“It’s become part of our standard of care,” Dr. Dolinger said. “This is now emerging in the United States and will soon take hold. There is a lot of interest.”

Dr. Dolinger is one of just a few American physicians credentialed by the International Bowel Ultrasound Group, an organization based out of Europe, Israel, and Canada. Formalized training and certification are necessary, Dr. Dolinger noted, to ensure that this new clinical approach maintains consistency as it is rolled out across the United States.

“We have the unique opportunity to do something from the ground up quickly, but also correctly, meaning that we can train everyone to speak the same language and do the same standardized exams so that all the findings and research are relatable,” Dr. Dolinger said.

He advised interested physicians to contact their local inflammatory bowel disease center to find out if training is available, and if it is, devoting “a lot of time” to the learning process.

“If you’re going to use this potentially as a clinical decision-making tool without using other invasive procedures, you really want to make sure what you’re doing is accurate and correct,” Dr. Dolinger said.

The investigators disclosed relationships with AbbVie, Merck, Takeda, and others. Dr. Dolinger disclosed a relationship with NeuroLogica, a subsidiary of Samsung Electronics.

Intestinal ultrasound (IUS) findings correlate strongly with endoscopy results in patients with ulcerative colitis (UC), with treatment responses detected as soon as 8 weeks after starting tofacitinib, a longitudinal prospective study has found.

IUS accurately detected improvements and remission across a variety of scoring methodologies, suggesting that it may be a cost-effective, noninvasive alternative to endoscopic monitoring, reported lead author Floris de Voogd, MD, of Amsterdam University Medical Centers, and colleagues.

“Endoscopy is generally considered as the gold standard for the diagnosis and follow-up of patients with UC,” the investigators wrote in Gastroenterology. “However, endoscopy is an invasive and costly modality and therefore less attractive to perform frequently during the disease course.”

Whereas noninvasive fecal biomarkers are a more economical method of monitoring inflammation and treatment responses, they fail to characterize disease extent and fall short in detecting early endoscopic responses, the investigators added.

The present study aimed to determine if IUS could offer more clinical insight by measuring bowel wall thickness. Thirty patients were enrolled with moderate to severe UC, all with an endoscopic Mayo score of at least 2. Twenty-seven of these patients were evaluable through follow-up, having undergone both IUS and endoscopy at baseline and 8 weeks after starting tofacitinib.

At both time points, IUS findings correlated significantly with endoscopic Mayo score (EMS), UC endoscopic index for severity, and Robarts Histopathology Index, with correlation coefficients of 0.68, 0.73, and 0.49, respectively. Remission according to EMS was defined as a score of 0, and improvement was defined as a score of 1 or less.

Patients with EMS improvement showed lower median bowel wall thickness in the sigmoid colon after 8 weeks of treatment than did patients without improvement (1.8 mm vs. 4.5 mm; P < .0001); patients who were in EMS remission after 8 weeks also had lower median bowel wall thickness of the sigmoid colon (1.4 mm vs. 4.0 mm; P = .016).

The investigators also sought to define cutoff values for bowel wall thickness. The most accurate cutoff values for identifying endoscopic remission and improvement were 2.8 mm (area under the receiver operating curve, 0.87; 95% confidence interval, 0.74-1.00; P = .006) and 3.9 mm (AUROC, 0.92; 95% CI, 0.82-1.00; P < .0001), respectively. Treatment response was best identified by a 32% threshold reduction in thickness (AUROC, 0.87; 95% CI, 0.74-1.00; P = .002).

“Intestinal ultrasound, with bowel wall thickness as the single most important parameter is accurate to determine treatment response to tofacitinib in patients with moderate-severe UC when compared against endoscopy,” the investigators concluded.

Michael Dolinger, MD, MBA, assistant professor of pediatrics and the associate pediatric gastroenterology fellowship program director at the Icahn School of Medicine at Mount Sinai, New York, said the study is noteworthy because it is the first of its kind to show that IUS can accurately monitor treatment responses in UC.

“This study is what we’re looking for now, and in the future,” Dr. Dolinger said in an interview. “We’re looking for noninvasive biomarkers to predict early responses so that we know as clinicians ... if our medicines are working or if we need to pivot and switch effectively.”

For patients, this can mean feeling better quicker while reducing burden of care, he added.

“We can use this study to predict patient responses without having to potentially rescope them in 8 weeks using a 5-minute point-of-care test in the clinic,” Dr. Dolinger said. “It’s huge to be able to say that for patients with colitis, and to provide reassurance that not only are they potentially feeling better, but the medicine is working to change and heal their bowel wall really quickly as well.”

Dr. Dolinger speaks from clinical experience. Over the past 2 years, he and his colleagues at Mount Sinai have been implementing IUS for patients with both UC and Crohn’s disease.

“It’s become part of our standard of care,” Dr. Dolinger said. “This is now emerging in the United States and will soon take hold. There is a lot of interest.”

Dr. Dolinger is one of just a few American physicians credentialed by the International Bowel Ultrasound Group, an organization based out of Europe, Israel, and Canada. Formalized training and certification are necessary, Dr. Dolinger noted, to ensure that this new clinical approach maintains consistency as it is rolled out across the United States.

“We have the unique opportunity to do something from the ground up quickly, but also correctly, meaning that we can train everyone to speak the same language and do the same standardized exams so that all the findings and research are relatable,” Dr. Dolinger said.

He advised interested physicians to contact their local inflammatory bowel disease center to find out if training is available, and if it is, devoting “a lot of time” to the learning process.

“If you’re going to use this potentially as a clinical decision-making tool without using other invasive procedures, you really want to make sure what you’re doing is accurate and correct,” Dr. Dolinger said.

The investigators disclosed relationships with AbbVie, Merck, Takeda, and others. Dr. Dolinger disclosed a relationship with NeuroLogica, a subsidiary of Samsung Electronics.

Caring for patients with short bowel syndrome (SBS) requires a multidisciplinary approach involving dietitians, nurses, surgeons, gastroenterologists or internists, and social workers experienced in SBS care, according to a clinical practice update expert review from the American Gastroenterological Association.

Kishore Iyer, MD, from Mount Sinai Hospital New York; John K. DiBaise, MD, from Mayo Clinic in Scottsdale, Ariz.; and Alberto Rubio-Tapia, MD, from the Cleveland Clinic, Ohio, developed 12 best practice advice statements based on available evidence. The items focus on adult patients with SBS; however, there was some overlap with the management of pediatric SBS. The review was published online in Clinical Gastroenterology and Hepatology.
 

Defining SBS

One update concerns defining SBS. The authors recommend that surgeons performing massive resections should report the residual bowel length, rather than the length of bowel resected.

“It is only the former that dictates outcome,” they wrote.

There is general agreement that a residual small intestinal length of 200 cm or less meets criteria for SBS. Measurement should be taken from “along the antimesenteric border of unstretched bowel, from the duodenojejunal flexure to the ileocecal junction, the site of any small bowel–colon anastomosis, or to the end-ostomy.”

Based on the residual bowel length, patients can be classified into three groups: end-jejunostomy, jejuno-colic, and jejuno-ileo-colic.
 

Assessing nutritional status

A dietitian experienced in SBS should perform a thorough nutritional assessment on all SBS patients. Long-term monitoring should include laboratory studies checking electrolytes and liver and kidney function, fluid balance, weight change, serum micronutrients, and bone density. Bone density should be repeated periodically, every 2-3 years.

Fluid and electrolyte problems may affect outcomes for SBS patients, particularly for those without a colon.
 

Adjusting diets

Most adult patients with SBS have significant malabsorption, so dietary intake “must be increased by at least 50% from their estimated needs,” the authors wrote. It’s best if the patient consumes the increased quantity throughout the day in 5-6 meals, they noted.

An experienced dietitian should counsel the patient based on the patient’s eating preferences. Incorporating preferences can help increase compliance with the adjustments that may become necessary based on symptoms, stool output, and weight.
 

Using pharmacologic therapy

Using antisecretory medications, including proton pump inhibitors or histamine-2 receptor antagonists, helps reduce gastric secretions, the damage of acid on the upper gut mucosa, and the function of pancreatic exocrine enzymes.

Antidiarrheals reduce intestinal motility but also cause a slight reduction in intestinal secretion. Common agents include loperamide, diphenoxylate with atropine, codeine, and tincture of opium. The review authors say loperamide should get preference over opiate drugs because it is not addictive or sedative.

Use of antidiarrheals should be guided by their effect on stool output.

“Loperamide and codeine may have a synergistic effect when used together,” the authors wrote.

Clonidine, which can be given transdermally, has also shown some benefit in treating high-output stool losses, presumably because of its effects on intestinal motility and secretion.

Weighing risks and benefits of teduglutide

The glucagonlike peptide–2 teduglutide is of particular interest for its ability to help improve intestinal absorption and hopefully wean patients off parenteral nutrition and some will achieve enteral autonomy, the authors wrote. “The very short half-life of native GLP-2 has been extended to allow daily subcutaneous injection in the recombinant molecule, teduglutide.”

However, because teduglutide is a growth factor and can boost the growth of polyps and cancer, it is contraindicated in patients with active gastrointestinal malignancies. Patients should undergo colonoscopy before treatment and periodically thereafter, the authors advised. The benefits of its use in patients with nongastrointestinal malignancy should be weighed carefully with these risks.

“The significant side effects of teduglutide and the cost mandate that teduglutide is employed only after optimizing diet and the more conventional SBS treatments described previously in carefully selected patients with [short bowel syndrome–intestinal failure],” the authors wrote.
 

Dosing drugs effectively

Medications in tablet form need to dissolve before being absorbed. Most oral medications are absorbed within the proximal jejunum, so they can be used in patients with SBS.

“However,” the authors noted, “sustained- and delayed-release medications should be avoided.”

They suggested that, when applicable, alternatives such as liquids and topical medications should be considered, as should the monitoring of medication levels in the blood.

If a patient does not respond, approaches to consider may include increasing a dose, changing dose frequency, or changing drug formulation or route of administration, such as intravenous, subcutaneous, or transdermal.
 

Including parenteral nutrition and oral rehydration

Almost all patients with SBS will need parenteral nutrition (PN) support following resection, and few will be able to stop it before discharge from the hospital.

“Although more than 50% of adults with SBS are able to be weaned completely from PN within 5 years of diagnosis, the probability of eliminating PN use is less than 6% if not successfully accomplished in the first 2 years following the individual’s last bowel resection,” the authors wrote.

For long-term PN, tunneled central venous catheters are preferred over peripherally inserted central venous catheters because of the higher risk of thrombosis and issues related to self-administration of PN with the central catheters. Also, tunneled catheters are preferred over totally implanted devices, or ports, for long-term patients because the main benefit of the port is not realized given that the device needs to be continually accessed and exchanged weekly.

“When calculating PN volume and content, changes in the patient’s weight, laboratory results, stool or ostomy output, urine output, and complaints of thirst should be monitored,” the authors noted.

The authors also discussed oral rehydration solution because patients lose more water and sodium from their stoma than they take in by mouth. Careful consideration of the glucose and sodium levels in oral fluids is important because inappropriate fluids will exacerbate fluid losses in SBS. For example, hypotonic (including water, tea, coffee, alcohol) and hypertonic (including fruit juices and sodas) solutions should be limited.

“A major misconception on the part of patients is that they should drink large quantities of water; however, this generally leads to an increase in ostomy output and creates a vicious cycle further exacerbating fluid and electrolyte disturbances,” they wrote, instead advising glucose–electrolyte rehydration solution to enhance absorption and reduce secretion.
 

Preventing complications

“A knowledge of these complications is critical for those caring for these patients to be able to not only identify and treat them when they occur but also to prevent their occurrence whenever possible,” the authors wrote. Although they considered it beyond the scope of the review to outline every complication, they indicated some complications and management strategies via an included table. These complications can include cirrhosis, osteoporosis, acute kidney disease, and central venous catheter–related infection or occlusion.

Considering further surgery or intestinal transplantation

The authors noted that any further surgery should be carefully considered, with the following three contexts having possible value: “(1) to recruit unused distal bowel, (2) to augment the function of residual bowel through specific lengthening and tapering operations, or (3) to slow intestinal transit.”

Surgeons involved in managing SBS may need to confront complex intra-abdominal problems such as massive desmoid tumors, mesenteric ischemia, or complex enterocutaneous fistulae; a multidisciplinary intestinal rehabilitation team may be better able to help these patients. The authors noted that care for patients starts even before the first operation, by taking every measure to avoid massive bowel resection and the resulting SBS.

The authors noted the importance of early referral for intestinal transplantation consideration for patients with refractory dependency on parenteral nutrition or even onset of parenteral nutrition failure, which refers to complications such as intestinal failure–associated liver disease.

“At present, nearly 50% of patients being considered for ITX are also requiring simultaneous liver replacement, indicating late referral for ITX,” they wrote, citing a data from a report by the Centers for Medicare and Medicaid.

They also noted that data have shown short- and medium-term outcomes are steadily improving; however, long-term outcomes have been challenged by opportunistic infections, long-term graft attrition, and other impediments that may be preventing early referral for intestinal transplantation.
 

Educating patients, caregivers

Long-term PN may restrict activity for patients, but patients and caregivers should know about some modifications.

One is to cycle the PN over 10-14 hours overnight to allow freedom from the infusion pump during the day. Infusion pumps can be programmable, and some can be carried in a backpack for infusing during the day.

Authors recommend patient support groups, such as the Oley Foundation, which can help with issues surrounding body image and travel.

Because of the relative rarity of SBS, nonspecialist physicians may care for patients without a dedicated multidisciplinary team and may need education support in managing patients with complex care needs. One source the authors recommend is the Learn Intestinal Failure Tele-ECHO (Expanding Community Healthcare Outcomes) (LIFT-ECHO) project. The LIFT-ECHO project has become an online educational community with case-based learning in SBS, intestinal failure, and PN.

The authors disclose relationships with Takeda, Zealand, VectivBio, Napo, and Hanmi.

Caring for patients with short bowel syndrome (SBS) requires a multidisciplinary approach involving dietitians, nurses, surgeons, gastroenterologists or internists, and social workers experienced in SBS care, according to a clinical practice update expert review from the American Gastroenterological Association.

Kishore Iyer, MD, from Mount Sinai Hospital New York; John K. DiBaise, MD, from Mayo Clinic in Scottsdale, Ariz.; and Alberto Rubio-Tapia, MD, from the Cleveland Clinic, Ohio, developed 12 best practice advice statements based on available evidence. The items focus on adult patients with SBS; however, there was some overlap with the management of pediatric SBS. The review was published online in Clinical Gastroenterology and Hepatology.
 

Defining SBS

One update concerns defining SBS. The authors recommend that surgeons performing massive resections should report the residual bowel length, rather than the length of bowel resected.

“It is only the former that dictates outcome,” they wrote.

There is general agreement that a residual small intestinal length of 200 cm or less meets criteria for SBS. Measurement should be taken from “along the antimesenteric border of unstretched bowel, from the duodenojejunal flexure to the ileocecal junction, the site of any small bowel–colon anastomosis, or to the end-ostomy.”

Based on the residual bowel length, patients can be classified into three groups: end-jejunostomy, jejuno-colic, and jejuno-ileo-colic.
 

Assessing nutritional status

A dietitian experienced in SBS should perform a thorough nutritional assessment on all SBS patients. Long-term monitoring should include laboratory studies checking electrolytes and liver and kidney function, fluid balance, weight change, serum micronutrients, and bone density. Bone density should be repeated periodically, every 2-3 years.

Fluid and electrolyte problems may affect outcomes for SBS patients, particularly for those without a colon.
 

Adjusting diets

Most adult patients with SBS have significant malabsorption, so dietary intake “must be increased by at least 50% from their estimated needs,” the authors wrote. It’s best if the patient consumes the increased quantity throughout the day in 5-6 meals, they noted.

An experienced dietitian should counsel the patient based on the patient’s eating preferences. Incorporating preferences can help increase compliance with the adjustments that may become necessary based on symptoms, stool output, and weight.
 

Using pharmacologic therapy

Using antisecretory medications, including proton pump inhibitors or histamine-2 receptor antagonists, helps reduce gastric secretions, the damage of acid on the upper gut mucosa, and the function of pancreatic exocrine enzymes.

Antidiarrheals reduce intestinal motility but also cause a slight reduction in intestinal secretion. Common agents include loperamide, diphenoxylate with atropine, codeine, and tincture of opium. The review authors say loperamide should get preference over opiate drugs because it is not addictive or sedative.

Use of antidiarrheals should be guided by their effect on stool output.

“Loperamide and codeine may have a synergistic effect when used together,” the authors wrote.

Clonidine, which can be given transdermally, has also shown some benefit in treating high-output stool losses, presumably because of its effects on intestinal motility and secretion.

Weighing risks and benefits of teduglutide

The glucagonlike peptide–2 teduglutide is of particular interest for its ability to help improve intestinal absorption and hopefully wean patients off parenteral nutrition and some will achieve enteral autonomy, the authors wrote. “The very short half-life of native GLP-2 has been extended to allow daily subcutaneous injection in the recombinant molecule, teduglutide.”

However, because teduglutide is a growth factor and can boost the growth of polyps and cancer, it is contraindicated in patients with active gastrointestinal malignancies. Patients should undergo colonoscopy before treatment and periodically thereafter, the authors advised. The benefits of its use in patients with nongastrointestinal malignancy should be weighed carefully with these risks.

“The significant side effects of teduglutide and the cost mandate that teduglutide is employed only after optimizing diet and the more conventional SBS treatments described previously in carefully selected patients with [short bowel syndrome–intestinal failure],” the authors wrote.
 

Dosing drugs effectively

Medications in tablet form need to dissolve before being absorbed. Most oral medications are absorbed within the proximal jejunum, so they can be used in patients with SBS.

“However,” the authors noted, “sustained- and delayed-release medications should be avoided.”

They suggested that, when applicable, alternatives such as liquids and topical medications should be considered, as should the monitoring of medication levels in the blood.

If a patient does not respond, approaches to consider may include increasing a dose, changing dose frequency, or changing drug formulation or route of administration, such as intravenous, subcutaneous, or transdermal.
 

Including parenteral nutrition and oral rehydration

Almost all patients with SBS will need parenteral nutrition (PN) support following resection, and few will be able to stop it before discharge from the hospital.

“Although more than 50% of adults with SBS are able to be weaned completely from PN within 5 years of diagnosis, the probability of eliminating PN use is less than 6% if not successfully accomplished in the first 2 years following the individual’s last bowel resection,” the authors wrote.

For long-term PN, tunneled central venous catheters are preferred over peripherally inserted central venous catheters because of the higher risk of thrombosis and issues related to self-administration of PN with the central catheters. Also, tunneled catheters are preferred over totally implanted devices, or ports, for long-term patients because the main benefit of the port is not realized given that the device needs to be continually accessed and exchanged weekly.

“When calculating PN volume and content, changes in the patient’s weight, laboratory results, stool or ostomy output, urine output, and complaints of thirst should be monitored,” the authors noted.

The authors also discussed oral rehydration solution because patients lose more water and sodium from their stoma than they take in by mouth. Careful consideration of the glucose and sodium levels in oral fluids is important because inappropriate fluids will exacerbate fluid losses in SBS. For example, hypotonic (including water, tea, coffee, alcohol) and hypertonic (including fruit juices and sodas) solutions should be limited.

“A major misconception on the part of patients is that they should drink large quantities of water; however, this generally leads to an increase in ostomy output and creates a vicious cycle further exacerbating fluid and electrolyte disturbances,” they wrote, instead advising glucose–electrolyte rehydration solution to enhance absorption and reduce secretion.
 

Preventing complications

“A knowledge of these complications is critical for those caring for these patients to be able to not only identify and treat them when they occur but also to prevent their occurrence whenever possible,” the authors wrote. Although they considered it beyond the scope of the review to outline every complication, they indicated some complications and management strategies via an included table. These complications can include cirrhosis, osteoporosis, acute kidney disease, and central venous catheter–related infection or occlusion.

Considering further surgery or intestinal transplantation

The authors noted that any further surgery should be carefully considered, with the following three contexts having possible value: “(1) to recruit unused distal bowel, (2) to augment the function of residual bowel through specific lengthening and tapering operations, or (3) to slow intestinal transit.”

Surgeons involved in managing SBS may need to confront complex intra-abdominal problems such as massive desmoid tumors, mesenteric ischemia, or complex enterocutaneous fistulae; a multidisciplinary intestinal rehabilitation team may be better able to help these patients. The authors noted that care for patients starts even before the first operation, by taking every measure to avoid massive bowel resection and the resulting SBS.

The authors noted the importance of early referral for intestinal transplantation consideration for patients with refractory dependency on parenteral nutrition or even onset of parenteral nutrition failure, which refers to complications such as intestinal failure–associated liver disease.

“At present, nearly 50% of patients being considered for ITX are also requiring simultaneous liver replacement, indicating late referral for ITX,” they wrote, citing a data from a report by the Centers for Medicare and Medicaid.

They also noted that data have shown short- and medium-term outcomes are steadily improving; however, long-term outcomes have been challenged by opportunistic infections, long-term graft attrition, and other impediments that may be preventing early referral for intestinal transplantation.
 

Educating patients, caregivers

Long-term PN may restrict activity for patients, but patients and caregivers should know about some modifications.

One is to cycle the PN over 10-14 hours overnight to allow freedom from the infusion pump during the day. Infusion pumps can be programmable, and some can be carried in a backpack for infusing during the day.

Authors recommend patient support groups, such as the Oley Foundation, which can help with issues surrounding body image and travel.

Because of the relative rarity of SBS, nonspecialist physicians may care for patients without a dedicated multidisciplinary team and may need education support in managing patients with complex care needs. One source the authors recommend is the Learn Intestinal Failure Tele-ECHO (Expanding Community Healthcare Outcomes) (LIFT-ECHO) project. The LIFT-ECHO project has become an online educational community with case-based learning in SBS, intestinal failure, and PN.

The authors disclose relationships with Takeda, Zealand, VectivBio, Napo, and Hanmi.

Caring for patients with short bowel syndrome (SBS) requires a multidisciplinary approach involving dietitians, nurses, surgeons, gastroenterologists or internists, and social workers experienced in SBS care, according to a clinical practice update expert review from the American Gastroenterological Association.

Kishore Iyer, MD, from Mount Sinai Hospital New York; John K. DiBaise, MD, from Mayo Clinic in Scottsdale, Ariz.; and Alberto Rubio-Tapia, MD, from the Cleveland Clinic, Ohio, developed 12 best practice advice statements based on available evidence. The items focus on adult patients with SBS; however, there was some overlap with the management of pediatric SBS. The review was published online in Clinical Gastroenterology and Hepatology.
 

Defining SBS

One update concerns defining SBS. The authors recommend that surgeons performing massive resections should report the residual bowel length, rather than the length of bowel resected.

“It is only the former that dictates outcome,” they wrote.

There is general agreement that a residual small intestinal length of 200 cm or less meets criteria for SBS. Measurement should be taken from “along the antimesenteric border of unstretched bowel, from the duodenojejunal flexure to the ileocecal junction, the site of any small bowel–colon anastomosis, or to the end-ostomy.”

Based on the residual bowel length, patients can be classified into three groups: end-jejunostomy, jejuno-colic, and jejuno-ileo-colic.
 

Assessing nutritional status

A dietitian experienced in SBS should perform a thorough nutritional assessment on all SBS patients. Long-term monitoring should include laboratory studies checking electrolytes and liver and kidney function, fluid balance, weight change, serum micronutrients, and bone density. Bone density should be repeated periodically, every 2-3 years.

Fluid and electrolyte problems may affect outcomes for SBS patients, particularly for those without a colon.
 

Adjusting diets

Most adult patients with SBS have significant malabsorption, so dietary intake “must be increased by at least 50% from their estimated needs,” the authors wrote. It’s best if the patient consumes the increased quantity throughout the day in 5-6 meals, they noted.

An experienced dietitian should counsel the patient based on the patient’s eating preferences. Incorporating preferences can help increase compliance with the adjustments that may become necessary based on symptoms, stool output, and weight.
 

Using pharmacologic therapy

Using antisecretory medications, including proton pump inhibitors or histamine-2 receptor antagonists, helps reduce gastric secretions, the damage of acid on the upper gut mucosa, and the function of pancreatic exocrine enzymes.

Antidiarrheals reduce intestinal motility but also cause a slight reduction in intestinal secretion. Common agents include loperamide, diphenoxylate with atropine, codeine, and tincture of opium. The review authors say loperamide should get preference over opiate drugs because it is not addictive or sedative.

Use of antidiarrheals should be guided by their effect on stool output.

“Loperamide and codeine may have a synergistic effect when used together,” the authors wrote.

Clonidine, which can be given transdermally, has also shown some benefit in treating high-output stool losses, presumably because of its effects on intestinal motility and secretion.

Weighing risks and benefits of teduglutide

The glucagonlike peptide–2 teduglutide is of particular interest for its ability to help improve intestinal absorption and hopefully wean patients off parenteral nutrition and some will achieve enteral autonomy, the authors wrote. “The very short half-life of native GLP-2 has been extended to allow daily subcutaneous injection in the recombinant molecule, teduglutide.”

However, because teduglutide is a growth factor and can boost the growth of polyps and cancer, it is contraindicated in patients with active gastrointestinal malignancies. Patients should undergo colonoscopy before treatment and periodically thereafter, the authors advised. The benefits of its use in patients with nongastrointestinal malignancy should be weighed carefully with these risks.

“The significant side effects of teduglutide and the cost mandate that teduglutide is employed only after optimizing diet and the more conventional SBS treatments described previously in carefully selected patients with [short bowel syndrome–intestinal failure],” the authors wrote.
 

Dosing drugs effectively

Medications in tablet form need to dissolve before being absorbed. Most oral medications are absorbed within the proximal jejunum, so they can be used in patients with SBS.

“However,” the authors noted, “sustained- and delayed-release medications should be avoided.”

They suggested that, when applicable, alternatives such as liquids and topical medications should be considered, as should the monitoring of medication levels in the blood.

If a patient does not respond, approaches to consider may include increasing a dose, changing dose frequency, or changing drug formulation or route of administration, such as intravenous, subcutaneous, or transdermal.
 

Including parenteral nutrition and oral rehydration

Almost all patients with SBS will need parenteral nutrition (PN) support following resection, and few will be able to stop it before discharge from the hospital.

“Although more than 50% of adults with SBS are able to be weaned completely from PN within 5 years of diagnosis, the probability of eliminating PN use is less than 6% if not successfully accomplished in the first 2 years following the individual’s last bowel resection,” the authors wrote.

For long-term PN, tunneled central venous catheters are preferred over peripherally inserted central venous catheters because of the higher risk of thrombosis and issues related to self-administration of PN with the central catheters. Also, tunneled catheters are preferred over totally implanted devices, or ports, for long-term patients because the main benefit of the port is not realized given that the device needs to be continually accessed and exchanged weekly.

“When calculating PN volume and content, changes in the patient’s weight, laboratory results, stool or ostomy output, urine output, and complaints of thirst should be monitored,” the authors noted.

The authors also discussed oral rehydration solution because patients lose more water and sodium from their stoma than they take in by mouth. Careful consideration of the glucose and sodium levels in oral fluids is important because inappropriate fluids will exacerbate fluid losses in SBS. For example, hypotonic (including water, tea, coffee, alcohol) and hypertonic (including fruit juices and sodas) solutions should be limited.

“A major misconception on the part of patients is that they should drink large quantities of water; however, this generally leads to an increase in ostomy output and creates a vicious cycle further exacerbating fluid and electrolyte disturbances,” they wrote, instead advising glucose–electrolyte rehydration solution to enhance absorption and reduce secretion.
 

Preventing complications

“A knowledge of these complications is critical for those caring for these patients to be able to not only identify and treat them when they occur but also to prevent their occurrence whenever possible,” the authors wrote. Although they considered it beyond the scope of the review to outline every complication, they indicated some complications and management strategies via an included table. These complications can include cirrhosis, osteoporosis, acute kidney disease, and central venous catheter–related infection or occlusion.

Considering further surgery or intestinal transplantation

The authors noted that any further surgery should be carefully considered, with the following three contexts having possible value: “(1) to recruit unused distal bowel, (2) to augment the function of residual bowel through specific lengthening and tapering operations, or (3) to slow intestinal transit.”

Surgeons involved in managing SBS may need to confront complex intra-abdominal problems such as massive desmoid tumors, mesenteric ischemia, or complex enterocutaneous fistulae; a multidisciplinary intestinal rehabilitation team may be better able to help these patients. The authors noted that care for patients starts even before the first operation, by taking every measure to avoid massive bowel resection and the resulting SBS.

The authors noted the importance of early referral for intestinal transplantation consideration for patients with refractory dependency on parenteral nutrition or even onset of parenteral nutrition failure, which refers to complications such as intestinal failure–associated liver disease.

“At present, nearly 50% of patients being considered for ITX are also requiring simultaneous liver replacement, indicating late referral for ITX,” they wrote, citing a data from a report by the Centers for Medicare and Medicaid.

They also noted that data have shown short- and medium-term outcomes are steadily improving; however, long-term outcomes have been challenged by opportunistic infections, long-term graft attrition, and other impediments that may be preventing early referral for intestinal transplantation.
 

Educating patients, caregivers

Long-term PN may restrict activity for patients, but patients and caregivers should know about some modifications.

One is to cycle the PN over 10-14 hours overnight to allow freedom from the infusion pump during the day. Infusion pumps can be programmable, and some can be carried in a backpack for infusing during the day.

Authors recommend patient support groups, such as the Oley Foundation, which can help with issues surrounding body image and travel.

Because of the relative rarity of SBS, nonspecialist physicians may care for patients without a dedicated multidisciplinary team and may need education support in managing patients with complex care needs. One source the authors recommend is the Learn Intestinal Failure Tele-ECHO (Expanding Community Healthcare Outcomes) (LIFT-ECHO) project. The LIFT-ECHO project has become an online educational community with case-based learning in SBS, intestinal failure, and PN.

The authors disclose relationships with Takeda, Zealand, VectivBio, Napo, and Hanmi.

Fecal and mucosal microbiota have been the focus of much research. A study by Hou and colleagues that showed distinct differences in the intestinal and fecal microbiomes of patients with constipation-predominant or diarrhea-predominant IBS, compared with healthy controls, highlights the importance of a balanced and diverse microbiome to maintain a healthy gut. The article notes specific genera of microbiota that were associated with intestinal pain. When microbiota diversity is limited, the incidence of IBS is increased. This reinforces the importance of promoting a healthy microbiome in all patients and appreciating the correlation of the microbiome with the development of IBS.

 Internet-based cognitive-behavioral therapy may make it easier for patients to obtain therapy services. Kim and colleagues have shown this to be a cost-effective and efficacious way to deliver care. This care improves the quality of life for patients with IBS and is an effective intervention that is readily available. During pandemic times, the forum of online care also provides a safe way to deliver therapy services without the burden of the patient needing to commute to clinic and potentially be exposed to infectious disease. Given the relationship between IBS and psychiatric diagnoses noted by Creed and colleagues, it seems important to extend the availability of therapeutic interventions to as many patients with IBS as possible.

Fecal and mucosal microbiota have been the focus of much research. A study by Hou and colleagues that showed distinct differences in the intestinal and fecal microbiomes of patients with constipation-predominant or diarrhea-predominant IBS, compared with healthy controls, highlights the importance of a balanced and diverse microbiome to maintain a healthy gut. The article notes specific genera of microbiota that were associated with intestinal pain. When microbiota diversity is limited, the incidence of IBS is increased. This reinforces the importance of promoting a healthy microbiome in all patients and appreciating the correlation of the microbiome with the development of IBS.

 Internet-based cognitive-behavioral therapy may make it easier for patients to obtain therapy services. Kim and colleagues have shown this to be a cost-effective and efficacious way to deliver care. This care improves the quality of life for patients with IBS and is an effective intervention that is readily available. During pandemic times, the forum of online care also provides a safe way to deliver therapy services without the burden of the patient needing to commute to clinic and potentially be exposed to infectious disease. Given the relationship between IBS and psychiatric diagnoses noted by Creed and colleagues, it seems important to extend the availability of therapeutic interventions to as many patients with IBS as possible.

Fecal and mucosal microbiota have been the focus of much research. A study by Hou and colleagues that showed distinct differences in the intestinal and fecal microbiomes of patients with constipation-predominant or diarrhea-predominant IBS, compared with healthy controls, highlights the importance of a balanced and diverse microbiome to maintain a healthy gut. The article notes specific genera of microbiota that were associated with intestinal pain. When microbiota diversity is limited, the incidence of IBS is increased. This reinforces the importance of promoting a healthy microbiome in all patients and appreciating the correlation of the microbiome with the development of IBS.

 Internet-based cognitive-behavioral therapy may make it easier for patients to obtain therapy services. Kim and colleagues have shown this to be a cost-effective and efficacious way to deliver care. This care improves the quality of life for patients with IBS and is an effective intervention that is readily available. During pandemic times, the forum of online care also provides a safe way to deliver therapy services without the burden of the patient needing to commute to clinic and potentially be exposed to infectious disease. Given the relationship between IBS and psychiatric diagnoses noted by Creed and colleagues, it seems important to extend the availability of therapeutic interventions to as many patients with IBS as possible.