IBD & Intestinal Disorders

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderate to severe ulcerative colitis in adults aged 18 years and older, according to a release from Janssen. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.

Olivier Le Moal/Getty Images

The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.

“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.

Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.

Full prescribing information is available on the Janssen website, as is the full press release regarding the approval

[email protected]

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderate to severe ulcerative colitis in adults aged 18 years and older, according to a release from Janssen. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.

Olivier Le Moal/Getty Images

The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.

“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.

Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.

Full prescribing information is available on the Janssen website, as is the full press release regarding the approval

[email protected]

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderate to severe ulcerative colitis in adults aged 18 years and older, according to a release from Janssen. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.

Olivier Le Moal/Getty Images

The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.

“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.

Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.

Full prescribing information is available on the Janssen website, as is the full press release regarding the approval

[email protected]

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

An online assessment tool can be used to identify patients with inflammatory bowel disease (IBD) who are receiving an excess of corticosteroids, and a quality improvement plan lowered the use of excess corticosteroids, according to recent research in the journal Alimentary Pharmacology & Therapeutics.

Since measurement of excess corticosteroid use can be measured through an online assessment tool in clinical practice and long-term corticosteroid use is associated with adverse outcomes, it may be a quality marker for patients with IBD, wrote Christian P. Selinger, MD, from the Leeds (England) Gastroenterology Institute and colleagues. “Such key performance indicators have previously been lacking in IBD, unlike other disease areas such as diabetes and cardiovascular disease.”

Over a period of 3 months, Dr. Selinger and colleagues collected prospective data from 2,385 patients with IBD at 19 centers in England, Wales, and Scotland who had received steroids within the last year. The researchers divided the centers into groups based on whether they participated in the quality improvement program (7 centers), were new to the process of collecting data on steroid use (11 centers), or did not participate in the program (1 center). The seven centers that participated in the intervention were part of an audit that began in 2017, while the other centers were evaluated over a 3-month period between April and July 2017. Patients were asked questions about their steroid use, including whether the steroids were prescribed for their IBD, how long the course of steroids was, how many courses of steroids they received, and if they were able to stop using steroids without their symptoms returning.

The researchers found 14.8% of patients had an excess of steroids or were dependent on steroids, and patients at centers that participated in the quality improvement programs had a lower rate of exposure (23.8% vs. 31.0%; P less than .001) and a lower rate of steroid excess (11.5% vs. 17.1%; P less than .001) than did patients at sites that did not participate in the program. Centers with the improvement program also had steroid use decrease over time, from 30.0% in 2015 to 23.8% in 2017 (P = .003), and steroid excess also decreased from 13.8% at those centers to 11.5% during that time (P equals .17). The researchers noted that, in over half of cases (50.7%), the steroid excess was “avoidable.”

In patients with Crohn’s disease, those who had reduced steroid excess were more likely to be part of an intervention center (odds ratio, 0.72; 95% confidence interval, 0.46-0.97), at a center with a multidisciplinary team (OR, 0.54; 95% CI, 0.20-0.86), or receiving maintenance anti–tumor necrosis factor therapy (OR, 0.61; 95% CI, 0.24-0.95); in contrast, patients who received aminosalicylate were more likely to have steroid excess (OR, 1.72; 95% CI, 1.24-2.09). Steroid excess in ulcerative colitis (UC) patients was more likely among those receiving thiopurine monotherapy (OR, 1.97; 95% CI, 1.19‐3.01), while UC patients at an intervention center were less likely to have steroid excess (OR; 0.72; 95% CI, 0.45‐0.95).

The researchers said the online assessment is limited in assessing the reason for steroid excess and is unable to consider variables such as patient age, sex, IBD phenotype, and disease duration, but is a “simple, pragmatic tool” that can be used in real time in a clinical setting.

“This advances the case for steroid excess as a potential key performance indicator of quality in an IBD service, although in order for clinicians to benchmark their service and provide targets for improvements, any numerical goal attached to this key performance indicator would require consideration of case mix. Further data, including from national and international contexts, is needed,” concluded Dr. Selinger and colleagues.

The authors reported AbbVie provided the funding to develop the steroid assessment tool, as well as honoraria for invited attendees of the quality improvement plan, which the company also sponsored.

To help your patients better understand their treatment options, share AGA’s IBD patient education, which is online at www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease. 

SOURCE: Selinger CP et al. Aliment Pharmacol Ther. 2019. doi: 10.1111/apt.15497.

An online assessment tool can be used to identify patients with inflammatory bowel disease (IBD) who are receiving an excess of corticosteroids, and a quality improvement plan lowered the use of excess corticosteroids, according to recent research in the journal Alimentary Pharmacology & Therapeutics.

Since measurement of excess corticosteroid use can be measured through an online assessment tool in clinical practice and long-term corticosteroid use is associated with adverse outcomes, it may be a quality marker for patients with IBD, wrote Christian P. Selinger, MD, from the Leeds (England) Gastroenterology Institute and colleagues. “Such key performance indicators have previously been lacking in IBD, unlike other disease areas such as diabetes and cardiovascular disease.”

Over a period of 3 months, Dr. Selinger and colleagues collected prospective data from 2,385 patients with IBD at 19 centers in England, Wales, and Scotland who had received steroids within the last year. The researchers divided the centers into groups based on whether they participated in the quality improvement program (7 centers), were new to the process of collecting data on steroid use (11 centers), or did not participate in the program (1 center). The seven centers that participated in the intervention were part of an audit that began in 2017, while the other centers were evaluated over a 3-month period between April and July 2017. Patients were asked questions about their steroid use, including whether the steroids were prescribed for their IBD, how long the course of steroids was, how many courses of steroids they received, and if they were able to stop using steroids without their symptoms returning.

The researchers found 14.8% of patients had an excess of steroids or were dependent on steroids, and patients at centers that participated in the quality improvement programs had a lower rate of exposure (23.8% vs. 31.0%; P less than .001) and a lower rate of steroid excess (11.5% vs. 17.1%; P less than .001) than did patients at sites that did not participate in the program. Centers with the improvement program also had steroid use decrease over time, from 30.0% in 2015 to 23.8% in 2017 (P = .003), and steroid excess also decreased from 13.8% at those centers to 11.5% during that time (P equals .17). The researchers noted that, in over half of cases (50.7%), the steroid excess was “avoidable.”

In patients with Crohn’s disease, those who had reduced steroid excess were more likely to be part of an intervention center (odds ratio, 0.72; 95% confidence interval, 0.46-0.97), at a center with a multidisciplinary team (OR, 0.54; 95% CI, 0.20-0.86), or receiving maintenance anti–tumor necrosis factor therapy (OR, 0.61; 95% CI, 0.24-0.95); in contrast, patients who received aminosalicylate were more likely to have steroid excess (OR, 1.72; 95% CI, 1.24-2.09). Steroid excess in ulcerative colitis (UC) patients was more likely among those receiving thiopurine monotherapy (OR, 1.97; 95% CI, 1.19‐3.01), while UC patients at an intervention center were less likely to have steroid excess (OR; 0.72; 95% CI, 0.45‐0.95).

The researchers said the online assessment is limited in assessing the reason for steroid excess and is unable to consider variables such as patient age, sex, IBD phenotype, and disease duration, but is a “simple, pragmatic tool” that can be used in real time in a clinical setting.

“This advances the case for steroid excess as a potential key performance indicator of quality in an IBD service, although in order for clinicians to benchmark their service and provide targets for improvements, any numerical goal attached to this key performance indicator would require consideration of case mix. Further data, including from national and international contexts, is needed,” concluded Dr. Selinger and colleagues.

The authors reported AbbVie provided the funding to develop the steroid assessment tool, as well as honoraria for invited attendees of the quality improvement plan, which the company also sponsored.

To help your patients better understand their treatment options, share AGA’s IBD patient education, which is online at www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease. 

SOURCE: Selinger CP et al. Aliment Pharmacol Ther. 2019. doi: 10.1111/apt.15497.

An online assessment tool can be used to identify patients with inflammatory bowel disease (IBD) who are receiving an excess of corticosteroids, and a quality improvement plan lowered the use of excess corticosteroids, according to recent research in the journal Alimentary Pharmacology & Therapeutics.

Since measurement of excess corticosteroid use can be measured through an online assessment tool in clinical practice and long-term corticosteroid use is associated with adverse outcomes, it may be a quality marker for patients with IBD, wrote Christian P. Selinger, MD, from the Leeds (England) Gastroenterology Institute and colleagues. “Such key performance indicators have previously been lacking in IBD, unlike other disease areas such as diabetes and cardiovascular disease.”

Over a period of 3 months, Dr. Selinger and colleagues collected prospective data from 2,385 patients with IBD at 19 centers in England, Wales, and Scotland who had received steroids within the last year. The researchers divided the centers into groups based on whether they participated in the quality improvement program (7 centers), were new to the process of collecting data on steroid use (11 centers), or did not participate in the program (1 center). The seven centers that participated in the intervention were part of an audit that began in 2017, while the other centers were evaluated over a 3-month period between April and July 2017. Patients were asked questions about their steroid use, including whether the steroids were prescribed for their IBD, how long the course of steroids was, how many courses of steroids they received, and if they were able to stop using steroids without their symptoms returning.

The researchers found 14.8% of patients had an excess of steroids or were dependent on steroids, and patients at centers that participated in the quality improvement programs had a lower rate of exposure (23.8% vs. 31.0%; P less than .001) and a lower rate of steroid excess (11.5% vs. 17.1%; P less than .001) than did patients at sites that did not participate in the program. Centers with the improvement program also had steroid use decrease over time, from 30.0% in 2015 to 23.8% in 2017 (P = .003), and steroid excess also decreased from 13.8% at those centers to 11.5% during that time (P equals .17). The researchers noted that, in over half of cases (50.7%), the steroid excess was “avoidable.”

In patients with Crohn’s disease, those who had reduced steroid excess were more likely to be part of an intervention center (odds ratio, 0.72; 95% confidence interval, 0.46-0.97), at a center with a multidisciplinary team (OR, 0.54; 95% CI, 0.20-0.86), or receiving maintenance anti–tumor necrosis factor therapy (OR, 0.61; 95% CI, 0.24-0.95); in contrast, patients who received aminosalicylate were more likely to have steroid excess (OR, 1.72; 95% CI, 1.24-2.09). Steroid excess in ulcerative colitis (UC) patients was more likely among those receiving thiopurine monotherapy (OR, 1.97; 95% CI, 1.19‐3.01), while UC patients at an intervention center were less likely to have steroid excess (OR; 0.72; 95% CI, 0.45‐0.95).

The researchers said the online assessment is limited in assessing the reason for steroid excess and is unable to consider variables such as patient age, sex, IBD phenotype, and disease duration, but is a “simple, pragmatic tool” that can be used in real time in a clinical setting.

“This advances the case for steroid excess as a potential key performance indicator of quality in an IBD service, although in order for clinicians to benchmark their service and provide targets for improvements, any numerical goal attached to this key performance indicator would require consideration of case mix. Further data, including from national and international contexts, is needed,” concluded Dr. Selinger and colleagues.

The authors reported AbbVie provided the funding to develop the steroid assessment tool, as well as honoraria for invited attendees of the quality improvement plan, which the company also sponsored.

To help your patients better understand their treatment options, share AGA’s IBD patient education, which is online at www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease. 

SOURCE: Selinger CP et al. Aliment Pharmacol Ther. 2019. doi: 10.1111/apt.15497.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

Clinical evidence supporting the use of alternative biologic treatments and regimens for ulcerative colitis in patients who are unable to receive anti–tumor necrosis factor (TNF) therapies is beginning to emerge.

In one of two such trials published in The New England Journal of Medicine on Sept. 26, 2019, researchers led by Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai, New York, and associates evaluated ustekinumab as an 8-week induction therapy and a 44-week maintenance therapy in patients with moderate to severe ulcerative colitis (N Engl J Med 2019 Sep 25 doi: 10/1056/NEJMoa1900750). For the phase 3 trial, known as UNIFI, researchers randomly assigned 961 patients to receive an intravenous induction dose of ustekinumab over the course of 8 weeks (320 to a dose of 130 mg and 322 to a weight-range–based dose that approximated 6 mg per kilogram of body weight), while the remaining 319 received placebo. Patients who responded to induction therapy were randomly assigned to a 44-week maintenance phase in which they received subcutaneous maintenance injections of 90 mg of ustekinumab (172 to injections every 12 weeks, 176 to injections every 8 weeks, and 175 to placebo). The primary endpoint for both phases of the trial was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

Dr. Sands and his colleagues found that at week 8, clinical remission was achieved in 15.6% of patients in the 130-mg ustekinumab infusion group, compared with 15.5% in the 6-mg per kg of body weight group, and 5.3% of those in the placebo group. “The percentages of patients who met major secondary endpoints or had histo-endoscopic mucosal healing were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote. “Through week 8, the median changes from baseline in the IBDQ [Inflammatory Bowel Disease Questionnaire] score were significantly greater in both ustekinumab groups than in the placebo group.”

Meanwhile, at week 44, clinical remission was achieved in 38.4% of patients in the group receiving 90-mg subcutaneous ustekinumab every 12 weeks, compared with 43.8% of those in the group receiving 90 mg every 8 weeks, and 24% of those in the placebo group. “The percentages of patients with maintenance of clinical response through week 44, endoscopic improvement at week 44, or corticosteroid-free clinical remission (with either definition of clinical remission) at week 44 were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote.

When they evaluated other endpoints, Dr. Sands and his colleagues observed that improvements in partial Mayo scores and reductions in serum and fecal concentrations of inflammatory biomarkers that occurred with induction were sustained through week 44. “Although our findings suggest that ustekinumab was effective in patients with or without previous treatment failure with biologics for both induction and maintenance therapy, the percentages of patients in whom each endpoint was achieved were lower across groups with previous treatment failure with biologics,” they wrote.

In the second study, known as VARSITY, researchers led by Dr. Sands conducted a randomized, phase 3b, head-to-head trial comparing vedolizumab with adalimumab in 769 adults with moderate to severe ulcerative colitis, in an effort to determine if vedolizumab is superior after 52 weeks of treatment (N Engl J Med 2019 Sep 25. doi: 10/1056/NEJMoa1905725). They assigned patients to receive IV infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). The primary endpoint was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

At week 52, the researchers found that 31.3% of patients in the vedolizumab group achieved clinical remission, compared with 22.5% of those in the adalimumab group, while a higher percentage of patients in the vedolizumab group demonstrated endoscopic involvement (the first secondary outcome), compared with their counterparts in the adalimumab group (39.7% vs. 27.7%, respectively). Treatment effects were more pronounced in patients who had not previously used a TNF inhibitor.

In contrast, Dr. Sands and colleagues reported that at week 52, corticosteroid-free clinical remission was observed in 12.6% of patients in the vedolizumab group, compared with 21.8% of their counterparts in the adalimumab group. “It is difficult to explain the inconsistency of the results between this secondary remission outcome and the primary remission outcome,” they wrote. “The trial did not require a specific schedule for corticosteroid tapering, which can vary among practitioners. However, this limitation should not have resulted in differential effects in the two treatment groups.”

They noted that dosing regimens used in VARSITY were based on a conservative approach and use according to U.S. labels. “Real-world studies have shown improved efficacy outcomes after dose intensification in both adalimumab and vedolizumab therapies,” they wrote. “Data from ongoing trials of adalimumab (NCT02065622) and vedolizumab (NCT03029143) may further characterize the effect of higher doses on efficacy outcomes.”

UNIFI was funded by Janssen Research and Development. Dr. Sands disclosed that the Icahn School of Medicine received an institutional grant from Janssen to conduct the study. VARSITY was funded with support from Takeda. Dr. Sands reported that he received grant support and consulting fees from Takeda. Dr. Sands and coauthors reported having financial ties to many other companies in the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Sands B et al. N Engl J Med. 2019 Sep 25 doi: 10/1056/NEJMoa1900750; N Engl J Med. 2019 Sep 25 doi:.10/1056/NEJMoa1905725.

Clinical evidence supporting the use of alternative biologic treatments and regimens for ulcerative colitis in patients who are unable to receive anti–tumor necrosis factor (TNF) therapies is beginning to emerge.

In one of two such trials published in The New England Journal of Medicine on Sept. 26, 2019, researchers led by Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai, New York, and associates evaluated ustekinumab as an 8-week induction therapy and a 44-week maintenance therapy in patients with moderate to severe ulcerative colitis (N Engl J Med 2019 Sep 25 doi: 10/1056/NEJMoa1900750). For the phase 3 trial, known as UNIFI, researchers randomly assigned 961 patients to receive an intravenous induction dose of ustekinumab over the course of 8 weeks (320 to a dose of 130 mg and 322 to a weight-range–based dose that approximated 6 mg per kilogram of body weight), while the remaining 319 received placebo. Patients who responded to induction therapy were randomly assigned to a 44-week maintenance phase in which they received subcutaneous maintenance injections of 90 mg of ustekinumab (172 to injections every 12 weeks, 176 to injections every 8 weeks, and 175 to placebo). The primary endpoint for both phases of the trial was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

Dr. Sands and his colleagues found that at week 8, clinical remission was achieved in 15.6% of patients in the 130-mg ustekinumab infusion group, compared with 15.5% in the 6-mg per kg of body weight group, and 5.3% of those in the placebo group. “The percentages of patients who met major secondary endpoints or had histo-endoscopic mucosal healing were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote. “Through week 8, the median changes from baseline in the IBDQ [Inflammatory Bowel Disease Questionnaire] score were significantly greater in both ustekinumab groups than in the placebo group.”

Meanwhile, at week 44, clinical remission was achieved in 38.4% of patients in the group receiving 90-mg subcutaneous ustekinumab every 12 weeks, compared with 43.8% of those in the group receiving 90 mg every 8 weeks, and 24% of those in the placebo group. “The percentages of patients with maintenance of clinical response through week 44, endoscopic improvement at week 44, or corticosteroid-free clinical remission (with either definition of clinical remission) at week 44 were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote.

When they evaluated other endpoints, Dr. Sands and his colleagues observed that improvements in partial Mayo scores and reductions in serum and fecal concentrations of inflammatory biomarkers that occurred with induction were sustained through week 44. “Although our findings suggest that ustekinumab was effective in patients with or without previous treatment failure with biologics for both induction and maintenance therapy, the percentages of patients in whom each endpoint was achieved were lower across groups with previous treatment failure with biologics,” they wrote.

In the second study, known as VARSITY, researchers led by Dr. Sands conducted a randomized, phase 3b, head-to-head trial comparing vedolizumab with adalimumab in 769 adults with moderate to severe ulcerative colitis, in an effort to determine if vedolizumab is superior after 52 weeks of treatment (N Engl J Med 2019 Sep 25. doi: 10/1056/NEJMoa1905725). They assigned patients to receive IV infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). The primary endpoint was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

At week 52, the researchers found that 31.3% of patients in the vedolizumab group achieved clinical remission, compared with 22.5% of those in the adalimumab group, while a higher percentage of patients in the vedolizumab group demonstrated endoscopic involvement (the first secondary outcome), compared with their counterparts in the adalimumab group (39.7% vs. 27.7%, respectively). Treatment effects were more pronounced in patients who had not previously used a TNF inhibitor.

In contrast, Dr. Sands and colleagues reported that at week 52, corticosteroid-free clinical remission was observed in 12.6% of patients in the vedolizumab group, compared with 21.8% of their counterparts in the adalimumab group. “It is difficult to explain the inconsistency of the results between this secondary remission outcome and the primary remission outcome,” they wrote. “The trial did not require a specific schedule for corticosteroid tapering, which can vary among practitioners. However, this limitation should not have resulted in differential effects in the two treatment groups.”

They noted that dosing regimens used in VARSITY were based on a conservative approach and use according to U.S. labels. “Real-world studies have shown improved efficacy outcomes after dose intensification in both adalimumab and vedolizumab therapies,” they wrote. “Data from ongoing trials of adalimumab (NCT02065622) and vedolizumab (NCT03029143) may further characterize the effect of higher doses on efficacy outcomes.”

UNIFI was funded by Janssen Research and Development. Dr. Sands disclosed that the Icahn School of Medicine received an institutional grant from Janssen to conduct the study. VARSITY was funded with support from Takeda. Dr. Sands reported that he received grant support and consulting fees from Takeda. Dr. Sands and coauthors reported having financial ties to many other companies in the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Sands B et al. N Engl J Med. 2019 Sep 25 doi: 10/1056/NEJMoa1900750; N Engl J Med. 2019 Sep 25 doi:.10/1056/NEJMoa1905725.

Clinical evidence supporting the use of alternative biologic treatments and regimens for ulcerative colitis in patients who are unable to receive anti–tumor necrosis factor (TNF) therapies is beginning to emerge.

In one of two such trials published in The New England Journal of Medicine on Sept. 26, 2019, researchers led by Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai, New York, and associates evaluated ustekinumab as an 8-week induction therapy and a 44-week maintenance therapy in patients with moderate to severe ulcerative colitis (N Engl J Med 2019 Sep 25 doi: 10/1056/NEJMoa1900750). For the phase 3 trial, known as UNIFI, researchers randomly assigned 961 patients to receive an intravenous induction dose of ustekinumab over the course of 8 weeks (320 to a dose of 130 mg and 322 to a weight-range–based dose that approximated 6 mg per kilogram of body weight), while the remaining 319 received placebo. Patients who responded to induction therapy were randomly assigned to a 44-week maintenance phase in which they received subcutaneous maintenance injections of 90 mg of ustekinumab (172 to injections every 12 weeks, 176 to injections every 8 weeks, and 175 to placebo). The primary endpoint for both phases of the trial was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

Dr. Sands and his colleagues found that at week 8, clinical remission was achieved in 15.6% of patients in the 130-mg ustekinumab infusion group, compared with 15.5% in the 6-mg per kg of body weight group, and 5.3% of those in the placebo group. “The percentages of patients who met major secondary endpoints or had histo-endoscopic mucosal healing were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote. “Through week 8, the median changes from baseline in the IBDQ [Inflammatory Bowel Disease Questionnaire] score were significantly greater in both ustekinumab groups than in the placebo group.”

Meanwhile, at week 44, clinical remission was achieved in 38.4% of patients in the group receiving 90-mg subcutaneous ustekinumab every 12 weeks, compared with 43.8% of those in the group receiving 90 mg every 8 weeks, and 24% of those in the placebo group. “The percentages of patients with maintenance of clinical response through week 44, endoscopic improvement at week 44, or corticosteroid-free clinical remission (with either definition of clinical remission) at week 44 were significantly higher in both ustekinumab groups than in the placebo group,” the researchers wrote.

When they evaluated other endpoints, Dr. Sands and his colleagues observed that improvements in partial Mayo scores and reductions in serum and fecal concentrations of inflammatory biomarkers that occurred with induction were sustained through week 44. “Although our findings suggest that ustekinumab was effective in patients with or without previous treatment failure with biologics for both induction and maintenance therapy, the percentages of patients in whom each endpoint was achieved were lower across groups with previous treatment failure with biologics,” they wrote.

In the second study, known as VARSITY, researchers led by Dr. Sands conducted a randomized, phase 3b, head-to-head trial comparing vedolizumab with adalimumab in 769 adults with moderate to severe ulcerative colitis, in an effort to determine if vedolizumab is superior after 52 weeks of treatment (N Engl J Med 2019 Sep 25. doi: 10/1056/NEJMoa1905725). They assigned patients to receive IV infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). The primary endpoint was clinical remission, defined as a total score of 2 or lower on the Mayo scale, and no subscore greater than 1 on any of the four Mayo scale components.

At week 52, the researchers found that 31.3% of patients in the vedolizumab group achieved clinical remission, compared with 22.5% of those in the adalimumab group, while a higher percentage of patients in the vedolizumab group demonstrated endoscopic involvement (the first secondary outcome), compared with their counterparts in the adalimumab group (39.7% vs. 27.7%, respectively). Treatment effects were more pronounced in patients who had not previously used a TNF inhibitor.

In contrast, Dr. Sands and colleagues reported that at week 52, corticosteroid-free clinical remission was observed in 12.6% of patients in the vedolizumab group, compared with 21.8% of their counterparts in the adalimumab group. “It is difficult to explain the inconsistency of the results between this secondary remission outcome and the primary remission outcome,” they wrote. “The trial did not require a specific schedule for corticosteroid tapering, which can vary among practitioners. However, this limitation should not have resulted in differential effects in the two treatment groups.”

They noted that dosing regimens used in VARSITY were based on a conservative approach and use according to U.S. labels. “Real-world studies have shown improved efficacy outcomes after dose intensification in both adalimumab and vedolizumab therapies,” they wrote. “Data from ongoing trials of adalimumab (NCT02065622) and vedolizumab (NCT03029143) may further characterize the effect of higher doses on efficacy outcomes.”

UNIFI was funded by Janssen Research and Development. Dr. Sands disclosed that the Icahn School of Medicine received an institutional grant from Janssen to conduct the study. VARSITY was funded with support from Takeda. Dr. Sands reported that he received grant support and consulting fees from Takeda. Dr. Sands and coauthors reported having financial ties to many other companies in the pharmaceutical and biotechnology industries.

[email protected]

SOURCE: Sands B et al. N Engl J Med. 2019 Sep 25 doi: 10/1056/NEJMoa1900750; N Engl J Med. 2019 Sep 25 doi:.10/1056/NEJMoa1905725.

The subcutaneous (SC) form of vedolizumab is effective, generally safe, and well tolerated as maintenance treatment following intravenous vedolizumab induction in patients with moderately to severely active ulcerative colitis, results from a phase 3, double-blind trial demonstrated.

“The route of drug administration can be an important determinant of a patient’s treatment experience, particularly for chronic diseases such as UC [ulcerative colitis],” investigators led by William J. Sandborn, MD, of the division of gastroenterology and hepatology at the University of California, San Diego, wrote in a study published online in Gastroenterology (doi: 10/1053/j.gastro.2019.08.027). “Intravenous administration of a biologic treatment requires the patient to set time aside and travel to a treatment center for an infusion. In addition, the greater use of a health care facility increases the direct costs of care. Some studies show that even with the option of self-injection some patients may still prefer an IV route of administration for the reassurance provided by the opportunity for interacting with a health care professional or because they are averse to self-injection. The availability of both an SC and IV injection of vedolizumab will enable patients to choose the route of administration for maintenance treatment.”

Between Dec. 18, 2015, and Aug. 21, 2018, Dr. Sandborn and colleagues at 141 sites in 29 countries enrolled 353 patients with moderate to severely active UC to receive IV vedolizumab 300 mg at weeks 0 and 2. At week 6, 216 patients who demonstrated clinical response were randomly assigned to maintenance treatment: 106 to SC vedolizumab 108 mg every 2 weeks, 54 to IV vedolizumab 300 mg every 8 weeks, and 56 to placebo. The study’s primary endpoint was clinical remission at week 52, which was defined as a total Mayo score of 2 or lower and no subscore greater than 1.

The mean age of patients was 40 years and 60% were male, and they had UC for a mean of 8 years. At week 52, the researchers found that clinical remission was achieved by 46.2% of patients in the SC vedolizumab group, compared with 42.6% of patients in the IV vedolizumab group and 14.3% of patients in the placebo group. In addition, patients in the SC vedolizumab group experienced significantly greater rates of endoscopic improvement and durable clinical response compared with those in the placebo group (P less than .001).

In terms of safety, injection-site reactions were noted by 10.4% of patients in the SC vedolizumab group (mostly rash, swelling, erythema, and pruritus), compared with 1.9% of patients in the IV vedolizumab group and in no patients in the placebo group. “No serious cases were reported for the AEs of special interest: hypersensitivity (including injection site reactions or infusion-related AEs), malignancies, and liver injury,” the researchers wrote. “There were no cases of PML [progressive multifocal leukoencephalopathy] and no deaths.” They acknowledged that the study’s sample size was smaller than the previous GEMINI pivotal trial for vedolizumab IV in ulcerative colitis (N Engl J Med 2013;369:699-710). “This limitation may have contributed to the findings of numerically greater but not statistically significant differences between treatment arms for some secondary endpoints such as durable clinical remission and corticosteroid-free clinical remission,” they wrote.

Takeda sponsored the study. Dr. Sandborn and coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Sandborn WJ et al. Gastroenterol 2019 Aug. 27. doi: 10/1053/j.gastro.2019.08.027.

The subcutaneous (SC) form of vedolizumab is effective, generally safe, and well tolerated as maintenance treatment following intravenous vedolizumab induction in patients with moderately to severely active ulcerative colitis, results from a phase 3, double-blind trial demonstrated.

“The route of drug administration can be an important determinant of a patient’s treatment experience, particularly for chronic diseases such as UC [ulcerative colitis],” investigators led by William J. Sandborn, MD, of the division of gastroenterology and hepatology at the University of California, San Diego, wrote in a study published online in Gastroenterology (doi: 10/1053/j.gastro.2019.08.027). “Intravenous administration of a biologic treatment requires the patient to set time aside and travel to a treatment center for an infusion. In addition, the greater use of a health care facility increases the direct costs of care. Some studies show that even with the option of self-injection some patients may still prefer an IV route of administration for the reassurance provided by the opportunity for interacting with a health care professional or because they are averse to self-injection. The availability of both an SC and IV injection of vedolizumab will enable patients to choose the route of administration for maintenance treatment.”

Between Dec. 18, 2015, and Aug. 21, 2018, Dr. Sandborn and colleagues at 141 sites in 29 countries enrolled 353 patients with moderate to severely active UC to receive IV vedolizumab 300 mg at weeks 0 and 2. At week 6, 216 patients who demonstrated clinical response were randomly assigned to maintenance treatment: 106 to SC vedolizumab 108 mg every 2 weeks, 54 to IV vedolizumab 300 mg every 8 weeks, and 56 to placebo. The study’s primary endpoint was clinical remission at week 52, which was defined as a total Mayo score of 2 or lower and no subscore greater than 1.

The mean age of patients was 40 years and 60% were male, and they had UC for a mean of 8 years. At week 52, the researchers found that clinical remission was achieved by 46.2% of patients in the SC vedolizumab group, compared with 42.6% of patients in the IV vedolizumab group and 14.3% of patients in the placebo group. In addition, patients in the SC vedolizumab group experienced significantly greater rates of endoscopic improvement and durable clinical response compared with those in the placebo group (P less than .001).

In terms of safety, injection-site reactions were noted by 10.4% of patients in the SC vedolizumab group (mostly rash, swelling, erythema, and pruritus), compared with 1.9% of patients in the IV vedolizumab group and in no patients in the placebo group. “No serious cases were reported for the AEs of special interest: hypersensitivity (including injection site reactions or infusion-related AEs), malignancies, and liver injury,” the researchers wrote. “There were no cases of PML [progressive multifocal leukoencephalopathy] and no deaths.” They acknowledged that the study’s sample size was smaller than the previous GEMINI pivotal trial for vedolizumab IV in ulcerative colitis (N Engl J Med 2013;369:699-710). “This limitation may have contributed to the findings of numerically greater but not statistically significant differences between treatment arms for some secondary endpoints such as durable clinical remission and corticosteroid-free clinical remission,” they wrote.

Takeda sponsored the study. Dr. Sandborn and coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Sandborn WJ et al. Gastroenterol 2019 Aug. 27. doi: 10/1053/j.gastro.2019.08.027.

The subcutaneous (SC) form of vedolizumab is effective, generally safe, and well tolerated as maintenance treatment following intravenous vedolizumab induction in patients with moderately to severely active ulcerative colitis, results from a phase 3, double-blind trial demonstrated.

“The route of drug administration can be an important determinant of a patient’s treatment experience, particularly for chronic diseases such as UC [ulcerative colitis],” investigators led by William J. Sandborn, MD, of the division of gastroenterology and hepatology at the University of California, San Diego, wrote in a study published online in Gastroenterology (doi: 10/1053/j.gastro.2019.08.027). “Intravenous administration of a biologic treatment requires the patient to set time aside and travel to a treatment center for an infusion. In addition, the greater use of a health care facility increases the direct costs of care. Some studies show that even with the option of self-injection some patients may still prefer an IV route of administration for the reassurance provided by the opportunity for interacting with a health care professional or because they are averse to self-injection. The availability of both an SC and IV injection of vedolizumab will enable patients to choose the route of administration for maintenance treatment.”

Between Dec. 18, 2015, and Aug. 21, 2018, Dr. Sandborn and colleagues at 141 sites in 29 countries enrolled 353 patients with moderate to severely active UC to receive IV vedolizumab 300 mg at weeks 0 and 2. At week 6, 216 patients who demonstrated clinical response were randomly assigned to maintenance treatment: 106 to SC vedolizumab 108 mg every 2 weeks, 54 to IV vedolizumab 300 mg every 8 weeks, and 56 to placebo. The study’s primary endpoint was clinical remission at week 52, which was defined as a total Mayo score of 2 or lower and no subscore greater than 1.

The mean age of patients was 40 years and 60% were male, and they had UC for a mean of 8 years. At week 52, the researchers found that clinical remission was achieved by 46.2% of patients in the SC vedolizumab group, compared with 42.6% of patients in the IV vedolizumab group and 14.3% of patients in the placebo group. In addition, patients in the SC vedolizumab group experienced significantly greater rates of endoscopic improvement and durable clinical response compared with those in the placebo group (P less than .001).

In terms of safety, injection-site reactions were noted by 10.4% of patients in the SC vedolizumab group (mostly rash, swelling, erythema, and pruritus), compared with 1.9% of patients in the IV vedolizumab group and in no patients in the placebo group. “No serious cases were reported for the AEs of special interest: hypersensitivity (including injection site reactions or infusion-related AEs), malignancies, and liver injury,” the researchers wrote. “There were no cases of PML [progressive multifocal leukoencephalopathy] and no deaths.” They acknowledged that the study’s sample size was smaller than the previous GEMINI pivotal trial for vedolizumab IV in ulcerative colitis (N Engl J Med 2013;369:699-710). “This limitation may have contributed to the findings of numerically greater but not statistically significant differences between treatment arms for some secondary endpoints such as durable clinical remission and corticosteroid-free clinical remission,” they wrote.

Takeda sponsored the study. Dr. Sandborn and coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Sandborn WJ et al. Gastroenterol 2019 Aug. 27. doi: 10/1053/j.gastro.2019.08.027.

The Food and Drug Administration has approved tenapanor (Ibsrela) for adults with irritable bowel syndrome with constipation (IBS-C), according to a release from the drug’s developer, Ardelyx. The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.

Olivier Le Moal/Getty Images

The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

The full prescribing information can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved tenapanor (Ibsrela) for adults with irritable bowel syndrome with constipation (IBS-C), according to a release from the drug’s developer, Ardelyx. The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.

Olivier Le Moal/Getty Images

The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

The full prescribing information can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved tenapanor (Ibsrela) for adults with irritable bowel syndrome with constipation (IBS-C), according to a release from the drug’s developer, Ardelyx. The approval is based on a pair of phase 3, randomized, double-blind, placebo-controlled trials in patients meeting the Rome III criteria for IBS-C. Both trials had identical 12-week treatment phases, while trial 1 had a 14-week continuation phase, and trial 2 included a 4-week withdrawal period. The primary endpoint was proportion of responders in the 12-week treatment period; this was defined as a 30% reduction in abdominal pain score and an increase of at least one complete spontaneous bowel movement on average weekly for at least 6 of the first 12 treatment weeks, compared with placebo. Both trials met this endpoint, with trial 1 showing a 37% response rate with treatment versus 24% with placebo, and trial 2 showing rates of 27% and 19%, respectively. Improvements were seen as early as week 1 and were maintained through the end of treatment.

Olivier Le Moal/Getty Images

The most common treatment-related adverse event was diarrhea, with severe diarrhea reported in 2.5% of treated patients versus 0.2% of placebo patients. Discontinuation rates were low. Tenapanor is contraindicated in IBS-C patients younger than 6 years because of concerns about dehydration, and use should be avoided in patients aged 6-12 years. Safety and efficacy has not been established in patients younger than 18 years. Tenapanor is also contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

The full prescribing information can be found on the FDA website.

[email protected]

Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.

“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).

More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.

The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.

In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.

SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.

Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.

“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).

More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.

The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.

In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.

SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.

Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.

“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).

More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.

The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.

In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.

SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.

Screening for colorectal cancer in patients with cystic fibrosis is cost effective, and should be started at a younger age and performed more often, new research suggests.

While colorectal cancer (CRC) screening traditionally begins at age 50 years in people at average risk for the disease, those at high risk usually begin undergoing colonoscopies at an earlier age. Patients with cystic fibrosis fall under the latter category, wrote Andrea Gini, of the department of public health at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues, with an incidence of CRC up to 30 times higher than the general population, but their shorter lifespan has led to a “different trade-off between the benefits and harms of CRC screening.”

Between 2000 and 2015, the median predicted survival age for patients with cystic fibrosis increased from 33.3 years to 41.7 years; this increased survival has brought increased risk for other diseases, particularly in the GI tract, Mr. Gini and colleagues wrote in Gastroenterology. By using the Microsimulation Screening Analysis–Colon model – a joint project between Erasmus Medical Center and Memorial Sloan Kettering Cancer Center in New York – the investigators assessed the cost-effectiveness of CRC screening in patients with cystic fibrosis.

Three cohorts of 10 million patients each were simulated, with one cohort having undergone transplant, one cohort not having transplant, and one cohort of individuals without cystic fibrosis. The simulated patient age was 30 years in 2017. A total of 76 different colonoscopy-screening strategies were assessed, with each differing in screening interval (3, 5, or 10 years for colonoscopy), age to start screening (30, 35, 40, 45, or 50 years), and age to end screening (55, 60, 65, 70, or 75 years). The optimal screening strategy was determined based on a willingness-to-pay threshold of $100,000 per life-year gained, the investigators wrote.

In the absence of screening, the mortality rate for nontransplant cystic fibrosis patients was 19.1 per 1,000 people, and the rate for cystic fibrosis patients who had undergone transplant was 22.3 per 1,000 people. The standard screening strategy prevented more than 73% of CRC deaths in the general population, 66% of deaths in nontransplant cystic fibrosis patients, and 36% of deaths in cystic fibrosis patients with transplant; however, the model predicted that only 22% of individuals who received a transplant and 36% of those who did not would reach the age of 50 years.

According to the model, the optimal colonoscopy-screening strategy for nontransplant patients was one screen every 5 years, starting at 40 and screening until the age of 75. The incremental cost-effectiveness ratio (ICER) was $84,000 per life-year gained; CRC incidence was reduced by 52% and CRC mortality was reduced by 79%. For transplant patients, the best strategy was one screen every 3 years between the ages of 35 and 55, which reduced CRC mortality by 82% at an ICER of $71,000 per life-year gained.

In a separate analysis of fecal immunochemical testing, a less-demanding alternative to colonoscopy, the optimal screening strategy was an annual test between the age of 35 and 75 years for nontransplant cystic fibrosis patients, for an ICER of $47,000 per life-year gained and a CRC mortality reduction of 78%. The best strategy for transplant patients was once a year between the ages of 30 and 60, which reduced CRC mortality by 77% at an ICER of $86,000 per life-year gained. While fecal immunochemical testing may be more cost effective than colonoscopy, “specific evidence of its performance in the cystic fibrosis population is required before considering this screening modality,” the investigators noted.

“This study indicates that there is benefit to earlier CRC screening in the cystic fibrosis population and [that it] can be done at acceptable costs,” the investigators wrote. “The findings of this analysis support clinicians, researchers, and policy makers who aim to define a tailored CRC screening for individuals with cystic fibrosis in the United States.”

The study was funded by the Cystic Fibrosis Foundation, the Cancer Intervention and Surveillance Modeling Network consortium, and Memorial Sloan Kettering Cancer Center. The investigators reported no conflicts of interest.

[email protected]

SOURCE: Gini A et al. Gastroenterology. 2017 Dec 27. doi: 10.1053/j.gastro.2017.12.011.

Screening for colorectal cancer in patients with cystic fibrosis is cost effective, and should be started at a younger age and performed more often, new research suggests.

While colorectal cancer (CRC) screening traditionally begins at age 50 years in people at average risk for the disease, those at high risk usually begin undergoing colonoscopies at an earlier age. Patients with cystic fibrosis fall under the latter category, wrote Andrea Gini, of the department of public health at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues, with an incidence of CRC up to 30 times higher than the general population, but their shorter lifespan has led to a “different trade-off between the benefits and harms of CRC screening.”

Between 2000 and 2015, the median predicted survival age for patients with cystic fibrosis increased from 33.3 years to 41.7 years; this increased survival has brought increased risk for other diseases, particularly in the GI tract, Mr. Gini and colleagues wrote in Gastroenterology. By using the Microsimulation Screening Analysis–Colon model – a joint project between Erasmus Medical Center and Memorial Sloan Kettering Cancer Center in New York – the investigators assessed the cost-effectiveness of CRC screening in patients with cystic fibrosis.

Three cohorts of 10 million patients each were simulated, with one cohort having undergone transplant, one cohort not having transplant, and one cohort of individuals without cystic fibrosis. The simulated patient age was 30 years in 2017. A total of 76 different colonoscopy-screening strategies were assessed, with each differing in screening interval (3, 5, or 10 years for colonoscopy), age to start screening (30, 35, 40, 45, or 50 years), and age to end screening (55, 60, 65, 70, or 75 years). The optimal screening strategy was determined based on a willingness-to-pay threshold of $100,000 per life-year gained, the investigators wrote.

In the absence of screening, the mortality rate for nontransplant cystic fibrosis patients was 19.1 per 1,000 people, and the rate for cystic fibrosis patients who had undergone transplant was 22.3 per 1,000 people. The standard screening strategy prevented more than 73% of CRC deaths in the general population, 66% of deaths in nontransplant cystic fibrosis patients, and 36% of deaths in cystic fibrosis patients with transplant; however, the model predicted that only 22% of individuals who received a transplant and 36% of those who did not would reach the age of 50 years.

According to the model, the optimal colonoscopy-screening strategy for nontransplant patients was one screen every 5 years, starting at 40 and screening until the age of 75. The incremental cost-effectiveness ratio (ICER) was $84,000 per life-year gained; CRC incidence was reduced by 52% and CRC mortality was reduced by 79%. For transplant patients, the best strategy was one screen every 3 years between the ages of 35 and 55, which reduced CRC mortality by 82% at an ICER of $71,000 per life-year gained.

In a separate analysis of fecal immunochemical testing, a less-demanding alternative to colonoscopy, the optimal screening strategy was an annual test between the age of 35 and 75 years for nontransplant cystic fibrosis patients, for an ICER of $47,000 per life-year gained and a CRC mortality reduction of 78%. The best strategy for transplant patients was once a year between the ages of 30 and 60, which reduced CRC mortality by 77% at an ICER of $86,000 per life-year gained. While fecal immunochemical testing may be more cost effective than colonoscopy, “specific evidence of its performance in the cystic fibrosis population is required before considering this screening modality,” the investigators noted.

“This study indicates that there is benefit to earlier CRC screening in the cystic fibrosis population and [that it] can be done at acceptable costs,” the investigators wrote. “The findings of this analysis support clinicians, researchers, and policy makers who aim to define a tailored CRC screening for individuals with cystic fibrosis in the United States.”

The study was funded by the Cystic Fibrosis Foundation, the Cancer Intervention and Surveillance Modeling Network consortium, and Memorial Sloan Kettering Cancer Center. The investigators reported no conflicts of interest.

[email protected]

SOURCE: Gini A et al. Gastroenterology. 2017 Dec 27. doi: 10.1053/j.gastro.2017.12.011.

Screening for colorectal cancer in patients with cystic fibrosis is cost effective, and should be started at a younger age and performed more often, new research suggests.

While colorectal cancer (CRC) screening traditionally begins at age 50 years in people at average risk for the disease, those at high risk usually begin undergoing colonoscopies at an earlier age. Patients with cystic fibrosis fall under the latter category, wrote Andrea Gini, of the department of public health at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues, with an incidence of CRC up to 30 times higher than the general population, but their shorter lifespan has led to a “different trade-off between the benefits and harms of CRC screening.”

Between 2000 and 2015, the median predicted survival age for patients with cystic fibrosis increased from 33.3 years to 41.7 years; this increased survival has brought increased risk for other diseases, particularly in the GI tract, Mr. Gini and colleagues wrote in Gastroenterology. By using the Microsimulation Screening Analysis–Colon model – a joint project between Erasmus Medical Center and Memorial Sloan Kettering Cancer Center in New York – the investigators assessed the cost-effectiveness of CRC screening in patients with cystic fibrosis.

Three cohorts of 10 million patients each were simulated, with one cohort having undergone transplant, one cohort not having transplant, and one cohort of individuals without cystic fibrosis. The simulated patient age was 30 years in 2017. A total of 76 different colonoscopy-screening strategies were assessed, with each differing in screening interval (3, 5, or 10 years for colonoscopy), age to start screening (30, 35, 40, 45, or 50 years), and age to end screening (55, 60, 65, 70, or 75 years). The optimal screening strategy was determined based on a willingness-to-pay threshold of $100,000 per life-year gained, the investigators wrote.

In the absence of screening, the mortality rate for nontransplant cystic fibrosis patients was 19.1 per 1,000 people, and the rate for cystic fibrosis patients who had undergone transplant was 22.3 per 1,000 people. The standard screening strategy prevented more than 73% of CRC deaths in the general population, 66% of deaths in nontransplant cystic fibrosis patients, and 36% of deaths in cystic fibrosis patients with transplant; however, the model predicted that only 22% of individuals who received a transplant and 36% of those who did not would reach the age of 50 years.

According to the model, the optimal colonoscopy-screening strategy for nontransplant patients was one screen every 5 years, starting at 40 and screening until the age of 75. The incremental cost-effectiveness ratio (ICER) was $84,000 per life-year gained; CRC incidence was reduced by 52% and CRC mortality was reduced by 79%. For transplant patients, the best strategy was one screen every 3 years between the ages of 35 and 55, which reduced CRC mortality by 82% at an ICER of $71,000 per life-year gained.

In a separate analysis of fecal immunochemical testing, a less-demanding alternative to colonoscopy, the optimal screening strategy was an annual test between the age of 35 and 75 years for nontransplant cystic fibrosis patients, for an ICER of $47,000 per life-year gained and a CRC mortality reduction of 78%. The best strategy for transplant patients was once a year between the ages of 30 and 60, which reduced CRC mortality by 77% at an ICER of $86,000 per life-year gained. While fecal immunochemical testing may be more cost effective than colonoscopy, “specific evidence of its performance in the cystic fibrosis population is required before considering this screening modality,” the investigators noted.

“This study indicates that there is benefit to earlier CRC screening in the cystic fibrosis population and [that it] can be done at acceptable costs,” the investigators wrote. “The findings of this analysis support clinicians, researchers, and policy makers who aim to define a tailored CRC screening for individuals with cystic fibrosis in the United States.”

The study was funded by the Cystic Fibrosis Foundation, the Cancer Intervention and Surveillance Modeling Network consortium, and Memorial Sloan Kettering Cancer Center. The investigators reported no conflicts of interest.

[email protected]

SOURCE: Gini A et al. Gastroenterology. 2017 Dec 27. doi: 10.1053/j.gastro.2017.12.011.

CHICAGO – Evidence suggests that diet may cause incident inflammatory bowel disease (IBD) and induce associated symptoms, according to a lecture delivered at Freston Conference 2019, sponsored by the American Gastroenterological Association.

Although the literature is highly consistent, it contains discordant findings, and many questions remain unanswered. “We need more rigorous studies, and particularly more interventions, to truly understand the role diet may play in patients with IBD,” said Ashwin N. Ananthakrishnan, MD, MPH, associate professor of medicine at Massachusetts General Hospital in Boston.
 

Food can cause symptoms in IBD

Many patients with IBD are convinced that their diet caused their disease. A relevant point for physicians to consider is that these patients are at least as likely as is the general population to have intolerance or sensitivity to food components such as lactose and gluten. In a prospective questionnaire of 400 consecutive patients with IBD in the United Kingdom, 48% expressed the belief that diet could initiate IBD, and 57% said that diet could trigger a flare-up. In addition, 60% of respondents reported worsening of symptoms after eating certain foods, and about two-thirds deprived themselves of their favorite foods to prevent relapses (Inflamm Bowel Dis. 2016;22[1]:164-70). A French study found similar results. “Clearly there’s something there,” said Dr. Ananthakrishnan. Patients’ beliefs about the relationship between food and their symptoms are not simply misconceptions, he added.

A Canadian study published in 2016 found that almost one-third of patients with IBD avoid many food groups. “But there is significant heterogeneity in the foods that are avoided, and sometimes we mistake this heterogeneity for a lack of association between diet and symptoms in IBD,” said Dr. Ananthakrishnan. A larger number of patients avoid certain foods during periods of active disease, which suggests that food exacerbates their symptoms, he added. The same study showed that patients with IBD have more restrictive diets than do community controls. Patients eat fewer fruits and vegetables and generally consume less iron-rich food and less protein-rich food than healthy controls. GI intolerance, rather than professional advice, is the most common reason that patients with IBD restrict their diets (JPEN J Parenter Enteral Nutr. 2016;40[3]:405-11.).

A cross-sectional survey of 130 patients with IBD and 70 controls yielded similar results. Among patients, GI symptoms that resulted from consuming foods were not related to disease activity, disease location, or prior surgery. Patients with IBD tended to have greater frequency of GI intolerance to foods than did controls (Scand J Gastroenterol. 1997;32[6]:569-71.).
 

Diet may cause intestinal inflammation

International research has recorded increases in the consumption of sugar and fat (particularly saturated fat) and concomitant decreases in fiber consumption during the past several decades. The incidence of IBD has increased in parallel with these dietary changes with a remarkably similar trajectory, said Dr. Ananthakrishnan. The correlation between dietary changes and IBD incidence “holds true even more strikingly in countries that are now experiencing Westernization,” he added. These countries have undergone more rapid dietary changes, and their IBD incidence has doubled or tripled. The transition to “less traditional diets” appears to promote intestinal inflammation, said Dr. Ananthakrishnan.

An analysis of data from the European Prospective Investigation into Cancer (EPIC) study found an association between high consumption of sugar and soft drinks, together with low consumption of vegetables, and risk of ulcerative colitis (Inflamm Bowel Dis. 2016;22[2]:345-54.). A subsequent analysis of data from two prospective Swedish cohorts, however, found no association between consumption of sugary beverages and risk of Crohn’s disease or ulcerative colitis (Clin Gastroenterol Hepatol. 2019;17[1]:123-9.).

Although the data on sugar are mixed, data on the association between other macronutrient groups and risk of IBD are more consistent. When Dr. Ananthakrishnan and colleagues examined data from the Nurses’ Health Study, they found that the highest quintile of dietary fiber intake was associated with a 40% reduction in risk of Crohn’s disease, compared with the lowest quintile. The observed reduction of risk seemed to be greatest for fiber derived from fruits. Fiber from cereals, whole grains, or legumes, however, did not affect risk of Crohn’s disease (Gastroenterology. 2013;145[5]:970-7.).

A separate analysis of the Nurses’ Health Study suggested that high intake of n-3 polyunsaturated fatty acids (PUFAs) and low intake of n-6 PUFAs was associated with a 31% reduction in risk of ulcerative colitis and a 15% reduction in the risk of Crohn’s disease. These data were consistent with a previous analysis of EPIC data that found that high intake of n-6 PUFAs was associated with increased risk of ulcerative colitis (Gut. 2009;58[12]:1606-11.). Other analyses indicate that genetic polymorphisms likely modify the association between PUFAs and risk of ulcerative colitis, said Dr. Ananthakrishnan. “There may be an additional layer of complexity beyond just measuring your dietary intake.”

In addition to macronutrients, micronutrients can modify a patient’s risk of ulcerative colitis or Crohn’s disease. When Dr. Ananthakrishnan and colleagues examined the Nurses’ Health Study, they found an inverse association between vitamin D intake and risk of Crohn’s disease (Gastroenterology. 2012;142[3]:482-9.). In a separate study, they found that a zinc intake greater than 16 mg/day was associated with reduced risk of Crohn’s disease (Int J Epidemiol. 2015;44[6]:1995-2005.).

Patients aged older than 40 years and patients of European ancestry tend to be overrepresented in cohort studies, which reduces the generalizability of their conclusions, said Dr. Ananthakrishnan. Furthermore, cohort studies have not produced consistent findings regarding the relationship between various dietary components and risk of IBD. Nevertheless, the data suggest that dietary patterns may be associated with incident Crohn’s disease or ulcerative colitis.

 

An influence of diet on IBD risk is plausible

One mechanism through which diet may exercise a causal influence on the risk of IBD is by affecting the microbiome. In 2011, investigators studied 98 healthy volunteers who answered questionnaires about their diet. The researchers also used 16s rDNA sequencing to characterize the population’s stool samples. A diet high in animal protein, amino acids, and saturated fats was associated with large populations of Bacteroides. A diet low in fat and in animal protein, but high in carbohydrates and simple sugars was associated with large populations of Prevotella. When the investigators conducted a controlled-feeding study of 10 patients, microbiome composition changed within 1 day of initiating a high-fat-and-low-fiber or a low-fat-and-high-fiber diet (Science. 2011;334[6052]:105-8.). A more recent study showed that the diversity of the microbiome increased with the adoption of an animal-based diet (Nature. 2014;505[7484]:559-63.).

Diet also may exert a causal influence on IBD risk by altering the intestinal barrier. In an experimental model, 5-mg/mL concentrations of fiber from plantain and broccoli significantly reduced the translocation of Escherichia coli through a human intestinal epithelial barrier (Gut. 2010;59[10]:1331-9.). Increased fiber intake may thus result in reduced intestinal inflammation, said Dr. Ananthakrishnan.

Observational and experimental evidence thus support an effect of diet on the risk of IBD, and experimental evidence indicates that this effect is biologically plausible. Nevertheless, “there are many missing links,” and further study will clarify the role of diet in IBD incidence, said Dr. Ananthakrishnan.

AGA offers education for your patients about IBD, including lifestyle and nutrition management, in the AGA GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease-ibd.

[email protected]

CHICAGO – Evidence suggests that diet may cause incident inflammatory bowel disease (IBD) and induce associated symptoms, according to a lecture delivered at Freston Conference 2019, sponsored by the American Gastroenterological Association.

Although the literature is highly consistent, it contains discordant findings, and many questions remain unanswered. “We need more rigorous studies, and particularly more interventions, to truly understand the role diet may play in patients with IBD,” said Ashwin N. Ananthakrishnan, MD, MPH, associate professor of medicine at Massachusetts General Hospital in Boston.
 

Food can cause symptoms in IBD

Many patients with IBD are convinced that their diet caused their disease. A relevant point for physicians to consider is that these patients are at least as likely as is the general population to have intolerance or sensitivity to food components such as lactose and gluten. In a prospective questionnaire of 400 consecutive patients with IBD in the United Kingdom, 48% expressed the belief that diet could initiate IBD, and 57% said that diet could trigger a flare-up. In addition, 60% of respondents reported worsening of symptoms after eating certain foods, and about two-thirds deprived themselves of their favorite foods to prevent relapses (Inflamm Bowel Dis. 2016;22[1]:164-70). A French study found similar results. “Clearly there’s something there,” said Dr. Ananthakrishnan. Patients’ beliefs about the relationship between food and their symptoms are not simply misconceptions, he added.

A Canadian study published in 2016 found that almost one-third of patients with IBD avoid many food groups. “But there is significant heterogeneity in the foods that are avoided, and sometimes we mistake this heterogeneity for a lack of association between diet and symptoms in IBD,” said Dr. Ananthakrishnan. A larger number of patients avoid certain foods during periods of active disease, which suggests that food exacerbates their symptoms, he added. The same study showed that patients with IBD have more restrictive diets than do community controls. Patients eat fewer fruits and vegetables and generally consume less iron-rich food and less protein-rich food than healthy controls. GI intolerance, rather than professional advice, is the most common reason that patients with IBD restrict their diets (JPEN J Parenter Enteral Nutr. 2016;40[3]:405-11.).

A cross-sectional survey of 130 patients with IBD and 70 controls yielded similar results. Among patients, GI symptoms that resulted from consuming foods were not related to disease activity, disease location, or prior surgery. Patients with IBD tended to have greater frequency of GI intolerance to foods than did controls (Scand J Gastroenterol. 1997;32[6]:569-71.).
 

Diet may cause intestinal inflammation

International research has recorded increases in the consumption of sugar and fat (particularly saturated fat) and concomitant decreases in fiber consumption during the past several decades. The incidence of IBD has increased in parallel with these dietary changes with a remarkably similar trajectory, said Dr. Ananthakrishnan. The correlation between dietary changes and IBD incidence “holds true even more strikingly in countries that are now experiencing Westernization,” he added. These countries have undergone more rapid dietary changes, and their IBD incidence has doubled or tripled. The transition to “less traditional diets” appears to promote intestinal inflammation, said Dr. Ananthakrishnan.

An analysis of data from the European Prospective Investigation into Cancer (EPIC) study found an association between high consumption of sugar and soft drinks, together with low consumption of vegetables, and risk of ulcerative colitis (Inflamm Bowel Dis. 2016;22[2]:345-54.). A subsequent analysis of data from two prospective Swedish cohorts, however, found no association between consumption of sugary beverages and risk of Crohn’s disease or ulcerative colitis (Clin Gastroenterol Hepatol. 2019;17[1]:123-9.).

Although the data on sugar are mixed, data on the association between other macronutrient groups and risk of IBD are more consistent. When Dr. Ananthakrishnan and colleagues examined data from the Nurses’ Health Study, they found that the highest quintile of dietary fiber intake was associated with a 40% reduction in risk of Crohn’s disease, compared with the lowest quintile. The observed reduction of risk seemed to be greatest for fiber derived from fruits. Fiber from cereals, whole grains, or legumes, however, did not affect risk of Crohn’s disease (Gastroenterology. 2013;145[5]:970-7.).

A separate analysis of the Nurses’ Health Study suggested that high intake of n-3 polyunsaturated fatty acids (PUFAs) and low intake of n-6 PUFAs was associated with a 31% reduction in risk of ulcerative colitis and a 15% reduction in the risk of Crohn’s disease. These data were consistent with a previous analysis of EPIC data that found that high intake of n-6 PUFAs was associated with increased risk of ulcerative colitis (Gut. 2009;58[12]:1606-11.). Other analyses indicate that genetic polymorphisms likely modify the association between PUFAs and risk of ulcerative colitis, said Dr. Ananthakrishnan. “There may be an additional layer of complexity beyond just measuring your dietary intake.”

In addition to macronutrients, micronutrients can modify a patient’s risk of ulcerative colitis or Crohn’s disease. When Dr. Ananthakrishnan and colleagues examined the Nurses’ Health Study, they found an inverse association between vitamin D intake and risk of Crohn’s disease (Gastroenterology. 2012;142[3]:482-9.). In a separate study, they found that a zinc intake greater than 16 mg/day was associated with reduced risk of Crohn’s disease (Int J Epidemiol. 2015;44[6]:1995-2005.).

Patients aged older than 40 years and patients of European ancestry tend to be overrepresented in cohort studies, which reduces the generalizability of their conclusions, said Dr. Ananthakrishnan. Furthermore, cohort studies have not produced consistent findings regarding the relationship between various dietary components and risk of IBD. Nevertheless, the data suggest that dietary patterns may be associated with incident Crohn’s disease or ulcerative colitis.

 

An influence of diet on IBD risk is plausible

One mechanism through which diet may exercise a causal influence on the risk of IBD is by affecting the microbiome. In 2011, investigators studied 98 healthy volunteers who answered questionnaires about their diet. The researchers also used 16s rDNA sequencing to characterize the population’s stool samples. A diet high in animal protein, amino acids, and saturated fats was associated with large populations of Bacteroides. A diet low in fat and in animal protein, but high in carbohydrates and simple sugars was associated with large populations of Prevotella. When the investigators conducted a controlled-feeding study of 10 patients, microbiome composition changed within 1 day of initiating a high-fat-and-low-fiber or a low-fat-and-high-fiber diet (Science. 2011;334[6052]:105-8.). A more recent study showed that the diversity of the microbiome increased with the adoption of an animal-based diet (Nature. 2014;505[7484]:559-63.).

Diet also may exert a causal influence on IBD risk by altering the intestinal barrier. In an experimental model, 5-mg/mL concentrations of fiber from plantain and broccoli significantly reduced the translocation of Escherichia coli through a human intestinal epithelial barrier (Gut. 2010;59[10]:1331-9.). Increased fiber intake may thus result in reduced intestinal inflammation, said Dr. Ananthakrishnan.

Observational and experimental evidence thus support an effect of diet on the risk of IBD, and experimental evidence indicates that this effect is biologically plausible. Nevertheless, “there are many missing links,” and further study will clarify the role of diet in IBD incidence, said Dr. Ananthakrishnan.

AGA offers education for your patients about IBD, including lifestyle and nutrition management, in the AGA GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease-ibd.

[email protected]

CHICAGO – Evidence suggests that diet may cause incident inflammatory bowel disease (IBD) and induce associated symptoms, according to a lecture delivered at Freston Conference 2019, sponsored by the American Gastroenterological Association.

Although the literature is highly consistent, it contains discordant findings, and many questions remain unanswered. “We need more rigorous studies, and particularly more interventions, to truly understand the role diet may play in patients with IBD,” said Ashwin N. Ananthakrishnan, MD, MPH, associate professor of medicine at Massachusetts General Hospital in Boston.
 

Food can cause symptoms in IBD

Many patients with IBD are convinced that their diet caused their disease. A relevant point for physicians to consider is that these patients are at least as likely as is the general population to have intolerance or sensitivity to food components such as lactose and gluten. In a prospective questionnaire of 400 consecutive patients with IBD in the United Kingdom, 48% expressed the belief that diet could initiate IBD, and 57% said that diet could trigger a flare-up. In addition, 60% of respondents reported worsening of symptoms after eating certain foods, and about two-thirds deprived themselves of their favorite foods to prevent relapses (Inflamm Bowel Dis. 2016;22[1]:164-70). A French study found similar results. “Clearly there’s something there,” said Dr. Ananthakrishnan. Patients’ beliefs about the relationship between food and their symptoms are not simply misconceptions, he added.

A Canadian study published in 2016 found that almost one-third of patients with IBD avoid many food groups. “But there is significant heterogeneity in the foods that are avoided, and sometimes we mistake this heterogeneity for a lack of association between diet and symptoms in IBD,” said Dr. Ananthakrishnan. A larger number of patients avoid certain foods during periods of active disease, which suggests that food exacerbates their symptoms, he added. The same study showed that patients with IBD have more restrictive diets than do community controls. Patients eat fewer fruits and vegetables and generally consume less iron-rich food and less protein-rich food than healthy controls. GI intolerance, rather than professional advice, is the most common reason that patients with IBD restrict their diets (JPEN J Parenter Enteral Nutr. 2016;40[3]:405-11.).

A cross-sectional survey of 130 patients with IBD and 70 controls yielded similar results. Among patients, GI symptoms that resulted from consuming foods were not related to disease activity, disease location, or prior surgery. Patients with IBD tended to have greater frequency of GI intolerance to foods than did controls (Scand J Gastroenterol. 1997;32[6]:569-71.).
 

Diet may cause intestinal inflammation

International research has recorded increases in the consumption of sugar and fat (particularly saturated fat) and concomitant decreases in fiber consumption during the past several decades. The incidence of IBD has increased in parallel with these dietary changes with a remarkably similar trajectory, said Dr. Ananthakrishnan. The correlation between dietary changes and IBD incidence “holds true even more strikingly in countries that are now experiencing Westernization,” he added. These countries have undergone more rapid dietary changes, and their IBD incidence has doubled or tripled. The transition to “less traditional diets” appears to promote intestinal inflammation, said Dr. Ananthakrishnan.

An analysis of data from the European Prospective Investigation into Cancer (EPIC) study found an association between high consumption of sugar and soft drinks, together with low consumption of vegetables, and risk of ulcerative colitis (Inflamm Bowel Dis. 2016;22[2]:345-54.). A subsequent analysis of data from two prospective Swedish cohorts, however, found no association between consumption of sugary beverages and risk of Crohn’s disease or ulcerative colitis (Clin Gastroenterol Hepatol. 2019;17[1]:123-9.).

Although the data on sugar are mixed, data on the association between other macronutrient groups and risk of IBD are more consistent. When Dr. Ananthakrishnan and colleagues examined data from the Nurses’ Health Study, they found that the highest quintile of dietary fiber intake was associated with a 40% reduction in risk of Crohn’s disease, compared with the lowest quintile. The observed reduction of risk seemed to be greatest for fiber derived from fruits. Fiber from cereals, whole grains, or legumes, however, did not affect risk of Crohn’s disease (Gastroenterology. 2013;145[5]:970-7.).

A separate analysis of the Nurses’ Health Study suggested that high intake of n-3 polyunsaturated fatty acids (PUFAs) and low intake of n-6 PUFAs was associated with a 31% reduction in risk of ulcerative colitis and a 15% reduction in the risk of Crohn’s disease. These data were consistent with a previous analysis of EPIC data that found that high intake of n-6 PUFAs was associated with increased risk of ulcerative colitis (Gut. 2009;58[12]:1606-11.). Other analyses indicate that genetic polymorphisms likely modify the association between PUFAs and risk of ulcerative colitis, said Dr. Ananthakrishnan. “There may be an additional layer of complexity beyond just measuring your dietary intake.”

In addition to macronutrients, micronutrients can modify a patient’s risk of ulcerative colitis or Crohn’s disease. When Dr. Ananthakrishnan and colleagues examined the Nurses’ Health Study, they found an inverse association between vitamin D intake and risk of Crohn’s disease (Gastroenterology. 2012;142[3]:482-9.). In a separate study, they found that a zinc intake greater than 16 mg/day was associated with reduced risk of Crohn’s disease (Int J Epidemiol. 2015;44[6]:1995-2005.).

Patients aged older than 40 years and patients of European ancestry tend to be overrepresented in cohort studies, which reduces the generalizability of their conclusions, said Dr. Ananthakrishnan. Furthermore, cohort studies have not produced consistent findings regarding the relationship between various dietary components and risk of IBD. Nevertheless, the data suggest that dietary patterns may be associated with incident Crohn’s disease or ulcerative colitis.

 

An influence of diet on IBD risk is plausible

One mechanism through which diet may exercise a causal influence on the risk of IBD is by affecting the microbiome. In 2011, investigators studied 98 healthy volunteers who answered questionnaires about their diet. The researchers also used 16s rDNA sequencing to characterize the population’s stool samples. A diet high in animal protein, amino acids, and saturated fats was associated with large populations of Bacteroides. A diet low in fat and in animal protein, but high in carbohydrates and simple sugars was associated with large populations of Prevotella. When the investigators conducted a controlled-feeding study of 10 patients, microbiome composition changed within 1 day of initiating a high-fat-and-low-fiber or a low-fat-and-high-fiber diet (Science. 2011;334[6052]:105-8.). A more recent study showed that the diversity of the microbiome increased with the adoption of an animal-based diet (Nature. 2014;505[7484]:559-63.).

Diet also may exert a causal influence on IBD risk by altering the intestinal barrier. In an experimental model, 5-mg/mL concentrations of fiber from plantain and broccoli significantly reduced the translocation of Escherichia coli through a human intestinal epithelial barrier (Gut. 2010;59[10]:1331-9.). Increased fiber intake may thus result in reduced intestinal inflammation, said Dr. Ananthakrishnan.

Observational and experimental evidence thus support an effect of diet on the risk of IBD, and experimental evidence indicates that this effect is biologically plausible. Nevertheless, “there are many missing links,” and further study will clarify the role of diet in IBD incidence, said Dr. Ananthakrishnan.

AGA offers education for your patients about IBD, including lifestyle and nutrition management, in the AGA GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/inflammatory-bowel-disease-ibd.

[email protected]