IBD & Intestinal Disorders

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting. “The answer now is totally yes.”

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), Dr. Khanna said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two that have completed phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroides and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with [ulcerative colitis] who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.

Help your patients understand their C. difficile diagnosis by sending them this resource from the AGA GI Patient Center.

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Get the latest information on the gut microbiome on the AGA website.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vedanta, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting. “The answer now is totally yes.”

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), Dr. Khanna said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two that have completed phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroides and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with [ulcerative colitis] who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.

Help your patients understand their C. difficile diagnosis by sending them this resource from the AGA GI Patient Center.

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Get the latest information on the gut microbiome on the AGA website.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vedanta, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting. “The answer now is totally yes.”

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), Dr. Khanna said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two that have completed phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroides and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with [ulcerative colitis] who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.

Help your patients understand their C. difficile diagnosis by sending them this resource from the AGA GI Patient Center.

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Get the latest information on the gut microbiome on the AGA website.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vedanta, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.

It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.

In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.

In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.

“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.

Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”

Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.

Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.

It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.

In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.

In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.

“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.

Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”

Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.

Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.

It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.

In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.

In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.

“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.

Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”

Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.

Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.

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

Bowel ultrasound predicts the clinical course of Crohn’s disease for up to 1 year, according to results of a prospective trial involving 225 patients.

After additional confirmation in larger studies, ultrasound could serve as a noninvasive alternative to colonoscopy for monitoring and predicting disease course, reported lead author Mariangela Allocca, MD, PhD, of Humanitas University, Milan, and colleagues.

“Frequent colonoscopies are expensive, invasive, and not well tolerated by patients, thus noninvasive tools for assessment and monitoring are strongly needed,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Bowel ultrasound accurately detects inflammatory bowel disease activity, extent, and complications, particularly in Crohn’s disease. Considering its low cost, minimal invasiveness ... and easy repeatability, bowel ultrasound may be a simple, readily available tool for assessing and monitoring Crohn’s disease.”

To test this hypothesis, Dr. Allocca and colleagues enrolled 225 consecutive patients with ileal and/or colonic Crohn’s disease diagnosed for at least 6 months and managed at a tertiary hospital in Italy. All patients underwent both colonoscopy and bowel ultrasound with no more than 3 months between each procedure.

Colonoscopy results were characterized by the Simplified Endoscopic Score for Crohn’s disease (SES-CD), whereas ultrasound was scored using a several parameters, including bowel wall pattern, bowel thickness, bowel wall flow, presence of complications (abscess, fistula, stricture), and characteristics of mesenteric lymph nodes and tissue. Ultrasound scores were considered high if they exceeded a cut-off of 3.52, which was determined by a receiver operating characteristic curve analysis.

Participants were followed for 12 months after baseline ultrasound. The primary objective was to determine the relationship between baseline ultrasound findings and negative disease course, defined by steroid usage, need for surgery, need for hospitalization, and/or change in therapy. The secondary objective was to understand the relationship between ultrasound findings and endoscopy activity.

Multivariable analysis revealed that ultrasound scores greater than 3.52 predicted a negative clinical disease course for up to one year (odds ratio, 6.97; 95% confidence interval, 2.87-16.93; P < .001), as did the presence of at least one disease complication at baseline (OR, 3.90; 95% CI, 1.21-12.53; P = 0.21). A worse clinical course at one-year was also predicted by a baseline fecal calprotectin value of at least 250 mcg/g (OR, 5.43; 95% CI, 2.25-13.11; P < .001) and male sex (OR, 2.60; 95% CI, 1.12-6.02; P = .025).

Investigators then assessed individual disease outcomes at 12 months and baseline results. For example, high ultrasound score and calprotectin at baseline each predicted the need for treatment escalation. In comparison, disease behavior (inflammatory, stricturing, penetrating) and C reactive protein predicted need for corticosteroids. The only significant predictor of hospitalization a year later was CRP.

“[B]owel ultrasound is able to predict disease course in Crohn’s disease patients,” they wrote. “It may identify patients at high risk of a negative course to adopt effective strategies to prevent any disease progression. Our data need to be confirmed and validated in further large studies.”

The investigators disclosed relationships with Janssen, AbbVie, Mundipharma, and others.

Bowel ultrasound predicts the clinical course of Crohn’s disease for up to 1 year, according to results of a prospective trial involving 225 patients.

After additional confirmation in larger studies, ultrasound could serve as a noninvasive alternative to colonoscopy for monitoring and predicting disease course, reported lead author Mariangela Allocca, MD, PhD, of Humanitas University, Milan, and colleagues.

“Frequent colonoscopies are expensive, invasive, and not well tolerated by patients, thus noninvasive tools for assessment and monitoring are strongly needed,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Bowel ultrasound accurately detects inflammatory bowel disease activity, extent, and complications, particularly in Crohn’s disease. Considering its low cost, minimal invasiveness ... and easy repeatability, bowel ultrasound may be a simple, readily available tool for assessing and monitoring Crohn’s disease.”

To test this hypothesis, Dr. Allocca and colleagues enrolled 225 consecutive patients with ileal and/or colonic Crohn’s disease diagnosed for at least 6 months and managed at a tertiary hospital in Italy. All patients underwent both colonoscopy and bowel ultrasound with no more than 3 months between each procedure.

Colonoscopy results were characterized by the Simplified Endoscopic Score for Crohn’s disease (SES-CD), whereas ultrasound was scored using a several parameters, including bowel wall pattern, bowel thickness, bowel wall flow, presence of complications (abscess, fistula, stricture), and characteristics of mesenteric lymph nodes and tissue. Ultrasound scores were considered high if they exceeded a cut-off of 3.52, which was determined by a receiver operating characteristic curve analysis.

Participants were followed for 12 months after baseline ultrasound. The primary objective was to determine the relationship between baseline ultrasound findings and negative disease course, defined by steroid usage, need for surgery, need for hospitalization, and/or change in therapy. The secondary objective was to understand the relationship between ultrasound findings and endoscopy activity.

Multivariable analysis revealed that ultrasound scores greater than 3.52 predicted a negative clinical disease course for up to one year (odds ratio, 6.97; 95% confidence interval, 2.87-16.93; P < .001), as did the presence of at least one disease complication at baseline (OR, 3.90; 95% CI, 1.21-12.53; P = 0.21). A worse clinical course at one-year was also predicted by a baseline fecal calprotectin value of at least 250 mcg/g (OR, 5.43; 95% CI, 2.25-13.11; P < .001) and male sex (OR, 2.60; 95% CI, 1.12-6.02; P = .025).

Investigators then assessed individual disease outcomes at 12 months and baseline results. For example, high ultrasound score and calprotectin at baseline each predicted the need for treatment escalation. In comparison, disease behavior (inflammatory, stricturing, penetrating) and C reactive protein predicted need for corticosteroids. The only significant predictor of hospitalization a year later was CRP.

“[B]owel ultrasound is able to predict disease course in Crohn’s disease patients,” they wrote. “It may identify patients at high risk of a negative course to adopt effective strategies to prevent any disease progression. Our data need to be confirmed and validated in further large studies.”

The investigators disclosed relationships with Janssen, AbbVie, Mundipharma, and others.

Bowel ultrasound predicts the clinical course of Crohn’s disease for up to 1 year, according to results of a prospective trial involving 225 patients.

After additional confirmation in larger studies, ultrasound could serve as a noninvasive alternative to colonoscopy for monitoring and predicting disease course, reported lead author Mariangela Allocca, MD, PhD, of Humanitas University, Milan, and colleagues.

“Frequent colonoscopies are expensive, invasive, and not well tolerated by patients, thus noninvasive tools for assessment and monitoring are strongly needed,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Bowel ultrasound accurately detects inflammatory bowel disease activity, extent, and complications, particularly in Crohn’s disease. Considering its low cost, minimal invasiveness ... and easy repeatability, bowel ultrasound may be a simple, readily available tool for assessing and monitoring Crohn’s disease.”

To test this hypothesis, Dr. Allocca and colleagues enrolled 225 consecutive patients with ileal and/or colonic Crohn’s disease diagnosed for at least 6 months and managed at a tertiary hospital in Italy. All patients underwent both colonoscopy and bowel ultrasound with no more than 3 months between each procedure.

Colonoscopy results were characterized by the Simplified Endoscopic Score for Crohn’s disease (SES-CD), whereas ultrasound was scored using a several parameters, including bowel wall pattern, bowel thickness, bowel wall flow, presence of complications (abscess, fistula, stricture), and characteristics of mesenteric lymph nodes and tissue. Ultrasound scores were considered high if they exceeded a cut-off of 3.52, which was determined by a receiver operating characteristic curve analysis.

Participants were followed for 12 months after baseline ultrasound. The primary objective was to determine the relationship between baseline ultrasound findings and negative disease course, defined by steroid usage, need for surgery, need for hospitalization, and/or change in therapy. The secondary objective was to understand the relationship between ultrasound findings and endoscopy activity.

Multivariable analysis revealed that ultrasound scores greater than 3.52 predicted a negative clinical disease course for up to one year (odds ratio, 6.97; 95% confidence interval, 2.87-16.93; P < .001), as did the presence of at least one disease complication at baseline (OR, 3.90; 95% CI, 1.21-12.53; P = 0.21). A worse clinical course at one-year was also predicted by a baseline fecal calprotectin value of at least 250 mcg/g (OR, 5.43; 95% CI, 2.25-13.11; P < .001) and male sex (OR, 2.60; 95% CI, 1.12-6.02; P = .025).

Investigators then assessed individual disease outcomes at 12 months and baseline results. For example, high ultrasound score and calprotectin at baseline each predicted the need for treatment escalation. In comparison, disease behavior (inflammatory, stricturing, penetrating) and C reactive protein predicted need for corticosteroids. The only significant predictor of hospitalization a year later was CRP.

“[B]owel ultrasound is able to predict disease course in Crohn’s disease patients,” they wrote. “It may identify patients at high risk of a negative course to adopt effective strategies to prevent any disease progression. Our data need to be confirmed and validated in further large studies.”

The investigators disclosed relationships with Janssen, AbbVie, Mundipharma, and others.

Three widely followed diets for nonconstipated irritable bowel syndrome (IBS) produce similar results, but traditional dietary advice (TDA) is easier to follow, researchers say.

“We recommend TDA as the first-choice dietary option due to its widespread availability and patient friendliness,” Anupam Rej, MBChB, from Teaching Hospitals NHS Foundation Trust in Sheffield, England, and colleagues write.

AlexRaths/Getty Images

They noted, however, that the low-FODMAP diet produced the most improvement in depression and dysphoria.

The study was published online in Clinical Gastroenterology and Hepatology.
 

What the dietary options entailed

The three diets have different origins and methodologies, but all are designed to reduce the abdominal pain, bloating, and altered bowel habits that characterize IBS.

TDA is based on recommendations of the UK National Institute for Health and Care Excellence and the British Dietetic Association. It includes “sensible eating patterns,” such as regular meals, never having too much or too little, and sufficient hydration. It calls for a reduction in alcoholic, caffeinated, and “fizzy” drinks; spicy, fatty, and processed foods; fresh fruit (a maximum of three per day); and fiber and other gas-producing foods, such as beans, bread, and sweeteners. It also asks people to address any perceived food intolerance, such as dairy.

In North America, the low-FODMAP diet is prescribed as first-line therapy, and the American College of Gastroenterology has given it a conditional recommendation.

FODMAPs are short-chain fermentable carbohydrates found in many fruits, vegetables, dairy products, artificial sweeteners, and wheat. They increase small intestinal water volume and colonic gas production that can induce gastrointestinal symptoms in people with visceral hypersensitivity.

People following the low-FODMAP diet start by eliminating all FODMAPs for 4-6 weeks, then gradually reintroducing them to determine which are most likely to trigger symptoms.

A gluten-free diet, inspired by what is prescribed to treat celiac disease, has gained popularity in recent years. Although researchers debate the mechanism by which this diet improves symptoms, one leading theory is a reduction in fructans that accompany gluten in foods such as bread.

A rare head-to-head comparison trial

The low-FODMAP diet has proved itself in more clinical trials than the other two approaches, but few, if any, trials have compared them head-to-head in a pragmatic randomized trial, Dr. Rej and colleagues found after reviewing the literature.

They set about filling this gap by recruiting 114 people with IBS and randomly assigning each of them to one of the diets. Ninety-nine people finished the trial, with 33 following each of the diets. People with IBS-constipation were excluded.

Participants were a mean age of 37 years. Seventy-one percent were female, and 88% were White. Their mean IBS symptom severity score was 301, with 9% rating their symptoms as mild, 47% as moderate, and 45% as severe.

The proportion who reported at least a 50% reduction in their symptoms was 58% for the gluten-free diet, 55% for the low-FODMAP diet, and 42% for the TDA. The differences in these proportions were not significant (P = .43).

The diets worked about as well regardless of whether the patients had IBS with diarrhea or IBS with mixed diarrhea and constipation.

More of the people on the low-FODMAP diet reported significant improvement in their depression and dysphoria than people on the other two diets.

Changes in anxiety, somatization, and other aspects of IBS quality of life didn’t differ significantly with diet.
 

Where the diets differ: cost and ease

Fewer people following the TDA rated it as expensive, difficult, or socially awkward, compared with the people following the other two diets.

More of those following the TDA and gluten-free diet found them easy to incorporate into their lives than those following the low-FODMAP diet. About two-thirds of the people in each of these groups said they would consider continuing their diets after the end of the study.

The proportion of people consuming the recommended dietary reference values for macronutrients did not change with any of the diets. However, those in the TDA group reduced their intake of potassium and iron. In the other groups, the researchers noted a reduction in thiamine and magnesium.

Because of COVID-19 restrictions, the researchers were able to collect stool samples from only half of participants. What they did collect showed no difference among the groups in dysbiosis index or functional bacterial profiles.

Baseline factors such as age, gender, IBS subtype, dysbiosis index, somatization, and mood did not predict response to the three diets.

Participants improved as much whether they received dietary instructions face-to-face or through a live virtual consultation.
 

Applications and limitations

At least one previous study showed that the low-FODMAP diet produced better results than the standard diets patients had been following, said Brian E. Lacy, MD, PhD, a professor of medicine at the Mayo Clinic in Jacksonville, Fla., who was not involved in the current study.

He agreed with the study’s conclusion that the TDA could be a good place for people with IBS to start.

“Based on their research, and the findings that patients thought the diet was less expensive, easier to follow, and easier to shop for, this is a reasonable approach,” he told this news organization. “However, if there’s no benefit with the traditional diet, then moving on to the more rigorous low-FODMAP diet makes sense to me.”

Study limitations include a short duration, lack of information about how patients can add foods back into their diet (particularly with the low-FODMAP diet), and insufficient sample size and lack of a placebo group contributing to an inability to detect all clinically significant differences among the diets, he said.

“Although this study is not definitive and doesn’t answer all key questions about which diet is best and how each performs in the long run, it does provide important information for patients and providers,” said Dr. Lacy.

The study was funded by Schaer. One of the study authors has reported receiving an educational grant from Schaer. Dr. Lacy has reported being on scientific advisory boards for Ironwood, Salix, and Allakos.

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

Three widely followed diets for nonconstipated irritable bowel syndrome (IBS) produce similar results, but traditional dietary advice (TDA) is easier to follow, researchers say.

“We recommend TDA as the first-choice dietary option due to its widespread availability and patient friendliness,” Anupam Rej, MBChB, from Teaching Hospitals NHS Foundation Trust in Sheffield, England, and colleagues write.

AlexRaths/Getty Images

They noted, however, that the low-FODMAP diet produced the most improvement in depression and dysphoria.

The study was published online in Clinical Gastroenterology and Hepatology.
 

What the dietary options entailed

The three diets have different origins and methodologies, but all are designed to reduce the abdominal pain, bloating, and altered bowel habits that characterize IBS.

TDA is based on recommendations of the UK National Institute for Health and Care Excellence and the British Dietetic Association. It includes “sensible eating patterns,” such as regular meals, never having too much or too little, and sufficient hydration. It calls for a reduction in alcoholic, caffeinated, and “fizzy” drinks; spicy, fatty, and processed foods; fresh fruit (a maximum of three per day); and fiber and other gas-producing foods, such as beans, bread, and sweeteners. It also asks people to address any perceived food intolerance, such as dairy.

In North America, the low-FODMAP diet is prescribed as first-line therapy, and the American College of Gastroenterology has given it a conditional recommendation.

FODMAPs are short-chain fermentable carbohydrates found in many fruits, vegetables, dairy products, artificial sweeteners, and wheat. They increase small intestinal water volume and colonic gas production that can induce gastrointestinal symptoms in people with visceral hypersensitivity.

People following the low-FODMAP diet start by eliminating all FODMAPs for 4-6 weeks, then gradually reintroducing them to determine which are most likely to trigger symptoms.

A gluten-free diet, inspired by what is prescribed to treat celiac disease, has gained popularity in recent years. Although researchers debate the mechanism by which this diet improves symptoms, one leading theory is a reduction in fructans that accompany gluten in foods such as bread.

A rare head-to-head comparison trial

The low-FODMAP diet has proved itself in more clinical trials than the other two approaches, but few, if any, trials have compared them head-to-head in a pragmatic randomized trial, Dr. Rej and colleagues found after reviewing the literature.

They set about filling this gap by recruiting 114 people with IBS and randomly assigning each of them to one of the diets. Ninety-nine people finished the trial, with 33 following each of the diets. People with IBS-constipation were excluded.

Participants were a mean age of 37 years. Seventy-one percent were female, and 88% were White. Their mean IBS symptom severity score was 301, with 9% rating their symptoms as mild, 47% as moderate, and 45% as severe.

The proportion who reported at least a 50% reduction in their symptoms was 58% for the gluten-free diet, 55% for the low-FODMAP diet, and 42% for the TDA. The differences in these proportions were not significant (P = .43).

The diets worked about as well regardless of whether the patients had IBS with diarrhea or IBS with mixed diarrhea and constipation.

More of the people on the low-FODMAP diet reported significant improvement in their depression and dysphoria than people on the other two diets.

Changes in anxiety, somatization, and other aspects of IBS quality of life didn’t differ significantly with diet.
 

Where the diets differ: cost and ease

Fewer people following the TDA rated it as expensive, difficult, or socially awkward, compared with the people following the other two diets.

More of those following the TDA and gluten-free diet found them easy to incorporate into their lives than those following the low-FODMAP diet. About two-thirds of the people in each of these groups said they would consider continuing their diets after the end of the study.

The proportion of people consuming the recommended dietary reference values for macronutrients did not change with any of the diets. However, those in the TDA group reduced their intake of potassium and iron. In the other groups, the researchers noted a reduction in thiamine and magnesium.

Because of COVID-19 restrictions, the researchers were able to collect stool samples from only half of participants. What they did collect showed no difference among the groups in dysbiosis index or functional bacterial profiles.

Baseline factors such as age, gender, IBS subtype, dysbiosis index, somatization, and mood did not predict response to the three diets.

Participants improved as much whether they received dietary instructions face-to-face or through a live virtual consultation.
 

Applications and limitations

At least one previous study showed that the low-FODMAP diet produced better results than the standard diets patients had been following, said Brian E. Lacy, MD, PhD, a professor of medicine at the Mayo Clinic in Jacksonville, Fla., who was not involved in the current study.

He agreed with the study’s conclusion that the TDA could be a good place for people with IBS to start.

“Based on their research, and the findings that patients thought the diet was less expensive, easier to follow, and easier to shop for, this is a reasonable approach,” he told this news organization. “However, if there’s no benefit with the traditional diet, then moving on to the more rigorous low-FODMAP diet makes sense to me.”

Study limitations include a short duration, lack of information about how patients can add foods back into their diet (particularly with the low-FODMAP diet), and insufficient sample size and lack of a placebo group contributing to an inability to detect all clinically significant differences among the diets, he said.

“Although this study is not definitive and doesn’t answer all key questions about which diet is best and how each performs in the long run, it does provide important information for patients and providers,” said Dr. Lacy.

The study was funded by Schaer. One of the study authors has reported receiving an educational grant from Schaer. Dr. Lacy has reported being on scientific advisory boards for Ironwood, Salix, and Allakos.

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

Three widely followed diets for nonconstipated irritable bowel syndrome (IBS) produce similar results, but traditional dietary advice (TDA) is easier to follow, researchers say.

“We recommend TDA as the first-choice dietary option due to its widespread availability and patient friendliness,” Anupam Rej, MBChB, from Teaching Hospitals NHS Foundation Trust in Sheffield, England, and colleagues write.

AlexRaths/Getty Images

They noted, however, that the low-FODMAP diet produced the most improvement in depression and dysphoria.

The study was published online in Clinical Gastroenterology and Hepatology.
 

What the dietary options entailed

The three diets have different origins and methodologies, but all are designed to reduce the abdominal pain, bloating, and altered bowel habits that characterize IBS.

TDA is based on recommendations of the UK National Institute for Health and Care Excellence and the British Dietetic Association. It includes “sensible eating patterns,” such as regular meals, never having too much or too little, and sufficient hydration. It calls for a reduction in alcoholic, caffeinated, and “fizzy” drinks; spicy, fatty, and processed foods; fresh fruit (a maximum of three per day); and fiber and other gas-producing foods, such as beans, bread, and sweeteners. It also asks people to address any perceived food intolerance, such as dairy.

In North America, the low-FODMAP diet is prescribed as first-line therapy, and the American College of Gastroenterology has given it a conditional recommendation.

FODMAPs are short-chain fermentable carbohydrates found in many fruits, vegetables, dairy products, artificial sweeteners, and wheat. They increase small intestinal water volume and colonic gas production that can induce gastrointestinal symptoms in people with visceral hypersensitivity.

People following the low-FODMAP diet start by eliminating all FODMAPs for 4-6 weeks, then gradually reintroducing them to determine which are most likely to trigger symptoms.

A gluten-free diet, inspired by what is prescribed to treat celiac disease, has gained popularity in recent years. Although researchers debate the mechanism by which this diet improves symptoms, one leading theory is a reduction in fructans that accompany gluten in foods such as bread.

A rare head-to-head comparison trial

The low-FODMAP diet has proved itself in more clinical trials than the other two approaches, but few, if any, trials have compared them head-to-head in a pragmatic randomized trial, Dr. Rej and colleagues found after reviewing the literature.

They set about filling this gap by recruiting 114 people with IBS and randomly assigning each of them to one of the diets. Ninety-nine people finished the trial, with 33 following each of the diets. People with IBS-constipation were excluded.

Participants were a mean age of 37 years. Seventy-one percent were female, and 88% were White. Their mean IBS symptom severity score was 301, with 9% rating their symptoms as mild, 47% as moderate, and 45% as severe.

The proportion who reported at least a 50% reduction in their symptoms was 58% for the gluten-free diet, 55% for the low-FODMAP diet, and 42% for the TDA. The differences in these proportions were not significant (P = .43).

The diets worked about as well regardless of whether the patients had IBS with diarrhea or IBS with mixed diarrhea and constipation.

More of the people on the low-FODMAP diet reported significant improvement in their depression and dysphoria than people on the other two diets.

Changes in anxiety, somatization, and other aspects of IBS quality of life didn’t differ significantly with diet.
 

Where the diets differ: cost and ease

Fewer people following the TDA rated it as expensive, difficult, or socially awkward, compared with the people following the other two diets.

More of those following the TDA and gluten-free diet found them easy to incorporate into their lives than those following the low-FODMAP diet. About two-thirds of the people in each of these groups said they would consider continuing their diets after the end of the study.

The proportion of people consuming the recommended dietary reference values for macronutrients did not change with any of the diets. However, those in the TDA group reduced their intake of potassium and iron. In the other groups, the researchers noted a reduction in thiamine and magnesium.

Because of COVID-19 restrictions, the researchers were able to collect stool samples from only half of participants. What they did collect showed no difference among the groups in dysbiosis index or functional bacterial profiles.

Baseline factors such as age, gender, IBS subtype, dysbiosis index, somatization, and mood did not predict response to the three diets.

Participants improved as much whether they received dietary instructions face-to-face or through a live virtual consultation.
 

Applications and limitations

At least one previous study showed that the low-FODMAP diet produced better results than the standard diets patients had been following, said Brian E. Lacy, MD, PhD, a professor of medicine at the Mayo Clinic in Jacksonville, Fla., who was not involved in the current study.

He agreed with the study’s conclusion that the TDA could be a good place for people with IBS to start.

“Based on their research, and the findings that patients thought the diet was less expensive, easier to follow, and easier to shop for, this is a reasonable approach,” he told this news organization. “However, if there’s no benefit with the traditional diet, then moving on to the more rigorous low-FODMAP diet makes sense to me.”

Study limitations include a short duration, lack of information about how patients can add foods back into their diet (particularly with the low-FODMAP diet), and insufficient sample size and lack of a placebo group contributing to an inability to detect all clinically significant differences among the diets, he said.

“Although this study is not definitive and doesn’t answer all key questions about which diet is best and how each performs in the long run, it does provide important information for patients and providers,” said Dr. Lacy.

The study was funded by Schaer. One of the study authors has reported receiving an educational grant from Schaer. Dr. Lacy has reported being on scientific advisory boards for Ironwood, Salix, and Allakos.

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

Both tofacitinib (Xeljanz) and vedolizumab (Entyvio) are effective options for people with ulcerative colitis (UC) who fail at least one antitumor necrosis factor (anti-TNF) therapy, a real-world study in France revealed.

However, response was superior with tofacitinib among people after primary failure to biologics and multiple therapeutic failure, the researchers report, including endoscopic improvement and mucosal healing.  

Anthony Buisson, MD, presented the results Feb. 18 at the 17th congress of the European Crohn’s and Colitis Organisation.
 

The French comparison

Although multiple therapeutic options are available to treat ulcerative colitis after anti-TNF failure, “there are no data comparing tofacitinib to vedolizumab in the real world,” said Dr. Buisson, a gastroenterologist at Clermont Auvergne University, Clermont-Ferrand, France.

In addition, network meta-analysis data are inconclusive, he said.

This led Dr. Buisson and colleagues to study adults with symptomatic UC with prior exposure to at least one anti-TNF treatment. They assessed 126 patients in a tofacitinib group and 178 in a vedolizumab group. The groups were comparable except for higher disease activity at baseline in the tofacitinib group.

The retrospective study was conducted at nine academic centers. Patients started either tofacitinib or vedolizumab between January 2019 and June 2021.

The primary endpoint, corticosteroid-free clinical remission at 16 weeks, was achieved by 45% of the tofacitinib group and 40% of the vedolizumab group. This difference was not statistically significant.

However, endoscopic improvement at week 16 did differ significantly and was achieved by 24% of the tofacitinib group versus 7% of the vedolizumab group (P = .0036).

“Tofacitinib and vedolizumab are effective to induce corticosteroid-free clinical remission at week 16 in patients with UC who failed at least one anti-TNF agent,” Dr. Buisson said.

“Vedolizumab seems to be less effective in cases of more severe UC and prior history of primary failure to any biologic,” he added.

Dr. Buisson said he and his colleagues plan to continue the study beyond 16 weeks to look at longterm outcomes.
 

The science from Spain

In another study presented at ECCO ‘22 Virtual, investigators from Spain compared vedolizumab to ustekinumab (Stelara) after at least one anti-TNF treatment failure, this time among people with Crohn’s disease.

Finding effective treatments after an anti-TNF failure is essential, Maria Jose Garcia, MD, said when presenting the results of the VERSUS-CD trial. “Over 20%-30% of Crohn’s disease patients are nonresponders or develop intolerance to anti-TNF therapies. Also, anti-TNF responders can experience a loss of response over time.”

Both vedolizumab and ustekinumab are effective for Crohn’s, she said. “But no clinical trial has compared both treatments, and limited data exist in real life.”

To remedy this situation, Dr. Garcia and colleagues studied 755 people from 30 medical centers in a national database in Spain who failed a previous anti-TNF agent, including 195 people switched to vedolizumab and 560 switched to ustekinumab. Luminal activity, perianal disease, or postoperative recurrence of Crohn’s were the indications for treatment.

The study’s main objective was to compare the short- and long-term treatment survival rate of vedolizumab and ustekinumab after anti-TNF therapy failure in clinical practice. Evaluating efficacy and safety were secondary aims.

“The treatment survival rate with ustekinumab was higher than with vedolizumab” over 5 years of follow-up, said Dr. Garcia, a gastroenterologist at Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain. The difference was statistically significant (P < .001).

Just less than half (43%) of the 327 patients discontinued treatment over time, including 142 in the vedolizumab group and 185 in the ustekinumab group. The most frequent cause was primarily nonresponse.

Infection, arthralgia, and infusion reactions were the most common adverse events. The safety profile was similar between groups, Dr. Garcia said.

“In clinical practice, vedolizumab and ustekinumab are both effective after anti-TNF failure or intolerance in CD,” Dr. Garcia said, adding that, “the retention rate of ustekinumab was higher compared to vedolizumab.”

When asked if the results will change how she practices, Dr. Garcia responded, “This confirms the first choice is ustekinumab more than vedolizumab in clinical practice, because it seems the clinical remission and durability of the treatment is superior.”
 

More options means more questions

“Looking back almost 25 years ago, the struggle was how to work with just one biologic and how to make it last for patients who have already failed all the available therapies. All these years later, we have such riches that the question we most often deal with is ‘What’s my first treatment?’ for patients with inflammatory bowel disease,” Arun Swaminath, MD, said, when asked to comment on both studies.

“Increasingly, we are seeing industry do head-to-head trials of drugs, but this is a time-consuming and expensive process,” added Dr. Swaminath, chief of gastroenterology and director of the inflammatory bowel diseases program at Lenox Hill Hospital, New York.

The study from Dr. Buisson and colleagues in UC approaches the design of a head-to-head trial, Dr. Swaminath said. “In the end, their primary endpoint was a statistical dead heat between the two options.”

In the VERSUS-CD study, vedolizumab was compared with ustekinumab, “with more patients not discontinuing ustekinumab therapy compared to vedolizumab,” he said. “This study also seems to favor sicker patients being treated with ustekinumab.”

“In both cases, we are starting to see the ‘order’ of treatments take shape, even before the benefit of head-to-head trials,” Dr. Swaminath said.

Dr. Buisson reports receiving grant support from AbbVie, Celltrion, Pfizer, and Takeda, as well as personal fees from AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Janssen, MSD, Nexbiome, Pfizer, Roche, sanofi-aventis, Takeda, Tillots, and Vifor Pharma. Dr. Garcia reports receiving financial support for traveling and educational activities from MSD, Janssen, AbbVie, Takeda, and Ferring. Dr. Swaminath reports receiving advanced IBD fellowship support from Janssen and Takeda and is on the advisory board for Boehringer Ingelheim.

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

Both tofacitinib (Xeljanz) and vedolizumab (Entyvio) are effective options for people with ulcerative colitis (UC) who fail at least one antitumor necrosis factor (anti-TNF) therapy, a real-world study in France revealed.

However, response was superior with tofacitinib among people after primary failure to biologics and multiple therapeutic failure, the researchers report, including endoscopic improvement and mucosal healing.  

Anthony Buisson, MD, presented the results Feb. 18 at the 17th congress of the European Crohn’s and Colitis Organisation.
 

The French comparison

Although multiple therapeutic options are available to treat ulcerative colitis after anti-TNF failure, “there are no data comparing tofacitinib to vedolizumab in the real world,” said Dr. Buisson, a gastroenterologist at Clermont Auvergne University, Clermont-Ferrand, France.

In addition, network meta-analysis data are inconclusive, he said.

This led Dr. Buisson and colleagues to study adults with symptomatic UC with prior exposure to at least one anti-TNF treatment. They assessed 126 patients in a tofacitinib group and 178 in a vedolizumab group. The groups were comparable except for higher disease activity at baseline in the tofacitinib group.

The retrospective study was conducted at nine academic centers. Patients started either tofacitinib or vedolizumab between January 2019 and June 2021.

The primary endpoint, corticosteroid-free clinical remission at 16 weeks, was achieved by 45% of the tofacitinib group and 40% of the vedolizumab group. This difference was not statistically significant.

However, endoscopic improvement at week 16 did differ significantly and was achieved by 24% of the tofacitinib group versus 7% of the vedolizumab group (P = .0036).

“Tofacitinib and vedolizumab are effective to induce corticosteroid-free clinical remission at week 16 in patients with UC who failed at least one anti-TNF agent,” Dr. Buisson said.

“Vedolizumab seems to be less effective in cases of more severe UC and prior history of primary failure to any biologic,” he added.

Dr. Buisson said he and his colleagues plan to continue the study beyond 16 weeks to look at longterm outcomes.
 

The science from Spain

In another study presented at ECCO ‘22 Virtual, investigators from Spain compared vedolizumab to ustekinumab (Stelara) after at least one anti-TNF treatment failure, this time among people with Crohn’s disease.

Finding effective treatments after an anti-TNF failure is essential, Maria Jose Garcia, MD, said when presenting the results of the VERSUS-CD trial. “Over 20%-30% of Crohn’s disease patients are nonresponders or develop intolerance to anti-TNF therapies. Also, anti-TNF responders can experience a loss of response over time.”

Both vedolizumab and ustekinumab are effective for Crohn’s, she said. “But no clinical trial has compared both treatments, and limited data exist in real life.”

To remedy this situation, Dr. Garcia and colleagues studied 755 people from 30 medical centers in a national database in Spain who failed a previous anti-TNF agent, including 195 people switched to vedolizumab and 560 switched to ustekinumab. Luminal activity, perianal disease, or postoperative recurrence of Crohn’s were the indications for treatment.

The study’s main objective was to compare the short- and long-term treatment survival rate of vedolizumab and ustekinumab after anti-TNF therapy failure in clinical practice. Evaluating efficacy and safety were secondary aims.

“The treatment survival rate with ustekinumab was higher than with vedolizumab” over 5 years of follow-up, said Dr. Garcia, a gastroenterologist at Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain. The difference was statistically significant (P < .001).

Just less than half (43%) of the 327 patients discontinued treatment over time, including 142 in the vedolizumab group and 185 in the ustekinumab group. The most frequent cause was primarily nonresponse.

Infection, arthralgia, and infusion reactions were the most common adverse events. The safety profile was similar between groups, Dr. Garcia said.

“In clinical practice, vedolizumab and ustekinumab are both effective after anti-TNF failure or intolerance in CD,” Dr. Garcia said, adding that, “the retention rate of ustekinumab was higher compared to vedolizumab.”

When asked if the results will change how she practices, Dr. Garcia responded, “This confirms the first choice is ustekinumab more than vedolizumab in clinical practice, because it seems the clinical remission and durability of the treatment is superior.”
 

More options means more questions

“Looking back almost 25 years ago, the struggle was how to work with just one biologic and how to make it last for patients who have already failed all the available therapies. All these years later, we have such riches that the question we most often deal with is ‘What’s my first treatment?’ for patients with inflammatory bowel disease,” Arun Swaminath, MD, said, when asked to comment on both studies.

“Increasingly, we are seeing industry do head-to-head trials of drugs, but this is a time-consuming and expensive process,” added Dr. Swaminath, chief of gastroenterology and director of the inflammatory bowel diseases program at Lenox Hill Hospital, New York.

The study from Dr. Buisson and colleagues in UC approaches the design of a head-to-head trial, Dr. Swaminath said. “In the end, their primary endpoint was a statistical dead heat between the two options.”

In the VERSUS-CD study, vedolizumab was compared with ustekinumab, “with more patients not discontinuing ustekinumab therapy compared to vedolizumab,” he said. “This study also seems to favor sicker patients being treated with ustekinumab.”

“In both cases, we are starting to see the ‘order’ of treatments take shape, even before the benefit of head-to-head trials,” Dr. Swaminath said.

Dr. Buisson reports receiving grant support from AbbVie, Celltrion, Pfizer, and Takeda, as well as personal fees from AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Janssen, MSD, Nexbiome, Pfizer, Roche, sanofi-aventis, Takeda, Tillots, and Vifor Pharma. Dr. Garcia reports receiving financial support for traveling and educational activities from MSD, Janssen, AbbVie, Takeda, and Ferring. Dr. Swaminath reports receiving advanced IBD fellowship support from Janssen and Takeda and is on the advisory board for Boehringer Ingelheim.

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

Both tofacitinib (Xeljanz) and vedolizumab (Entyvio) are effective options for people with ulcerative colitis (UC) who fail at least one antitumor necrosis factor (anti-TNF) therapy, a real-world study in France revealed.

However, response was superior with tofacitinib among people after primary failure to biologics and multiple therapeutic failure, the researchers report, including endoscopic improvement and mucosal healing.  

Anthony Buisson, MD, presented the results Feb. 18 at the 17th congress of the European Crohn’s and Colitis Organisation.
 

The French comparison

Although multiple therapeutic options are available to treat ulcerative colitis after anti-TNF failure, “there are no data comparing tofacitinib to vedolizumab in the real world,” said Dr. Buisson, a gastroenterologist at Clermont Auvergne University, Clermont-Ferrand, France.

In addition, network meta-analysis data are inconclusive, he said.

This led Dr. Buisson and colleagues to study adults with symptomatic UC with prior exposure to at least one anti-TNF treatment. They assessed 126 patients in a tofacitinib group and 178 in a vedolizumab group. The groups were comparable except for higher disease activity at baseline in the tofacitinib group.

The retrospective study was conducted at nine academic centers. Patients started either tofacitinib or vedolizumab between January 2019 and June 2021.

The primary endpoint, corticosteroid-free clinical remission at 16 weeks, was achieved by 45% of the tofacitinib group and 40% of the vedolizumab group. This difference was not statistically significant.

However, endoscopic improvement at week 16 did differ significantly and was achieved by 24% of the tofacitinib group versus 7% of the vedolizumab group (P = .0036).

“Tofacitinib and vedolizumab are effective to induce corticosteroid-free clinical remission at week 16 in patients with UC who failed at least one anti-TNF agent,” Dr. Buisson said.

“Vedolizumab seems to be less effective in cases of more severe UC and prior history of primary failure to any biologic,” he added.

Dr. Buisson said he and his colleagues plan to continue the study beyond 16 weeks to look at longterm outcomes.
 

The science from Spain

In another study presented at ECCO ‘22 Virtual, investigators from Spain compared vedolizumab to ustekinumab (Stelara) after at least one anti-TNF treatment failure, this time among people with Crohn’s disease.

Finding effective treatments after an anti-TNF failure is essential, Maria Jose Garcia, MD, said when presenting the results of the VERSUS-CD trial. “Over 20%-30% of Crohn’s disease patients are nonresponders or develop intolerance to anti-TNF therapies. Also, anti-TNF responders can experience a loss of response over time.”

Both vedolizumab and ustekinumab are effective for Crohn’s, she said. “But no clinical trial has compared both treatments, and limited data exist in real life.”

To remedy this situation, Dr. Garcia and colleagues studied 755 people from 30 medical centers in a national database in Spain who failed a previous anti-TNF agent, including 195 people switched to vedolizumab and 560 switched to ustekinumab. Luminal activity, perianal disease, or postoperative recurrence of Crohn’s were the indications for treatment.

The study’s main objective was to compare the short- and long-term treatment survival rate of vedolizumab and ustekinumab after anti-TNF therapy failure in clinical practice. Evaluating efficacy and safety were secondary aims.

“The treatment survival rate with ustekinumab was higher than with vedolizumab” over 5 years of follow-up, said Dr. Garcia, a gastroenterologist at Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain. The difference was statistically significant (P < .001).

Just less than half (43%) of the 327 patients discontinued treatment over time, including 142 in the vedolizumab group and 185 in the ustekinumab group. The most frequent cause was primarily nonresponse.

Infection, arthralgia, and infusion reactions were the most common adverse events. The safety profile was similar between groups, Dr. Garcia said.

“In clinical practice, vedolizumab and ustekinumab are both effective after anti-TNF failure or intolerance in CD,” Dr. Garcia said, adding that, “the retention rate of ustekinumab was higher compared to vedolizumab.”

When asked if the results will change how she practices, Dr. Garcia responded, “This confirms the first choice is ustekinumab more than vedolizumab in clinical practice, because it seems the clinical remission and durability of the treatment is superior.”
 

More options means more questions

“Looking back almost 25 years ago, the struggle was how to work with just one biologic and how to make it last for patients who have already failed all the available therapies. All these years later, we have such riches that the question we most often deal with is ‘What’s my first treatment?’ for patients with inflammatory bowel disease,” Arun Swaminath, MD, said, when asked to comment on both studies.

“Increasingly, we are seeing industry do head-to-head trials of drugs, but this is a time-consuming and expensive process,” added Dr. Swaminath, chief of gastroenterology and director of the inflammatory bowel diseases program at Lenox Hill Hospital, New York.

The study from Dr. Buisson and colleagues in UC approaches the design of a head-to-head trial, Dr. Swaminath said. “In the end, their primary endpoint was a statistical dead heat between the two options.”

In the VERSUS-CD study, vedolizumab was compared with ustekinumab, “with more patients not discontinuing ustekinumab therapy compared to vedolizumab,” he said. “This study also seems to favor sicker patients being treated with ustekinumab.”

“In both cases, we are starting to see the ‘order’ of treatments take shape, even before the benefit of head-to-head trials,” Dr. Swaminath said.

Dr. Buisson reports receiving grant support from AbbVie, Celltrion, Pfizer, and Takeda, as well as personal fees from AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Janssen, MSD, Nexbiome, Pfizer, Roche, sanofi-aventis, Takeda, Tillots, and Vifor Pharma. Dr. Garcia reports receiving financial support for traveling and educational activities from MSD, Janssen, AbbVie, Takeda, and Ferring. Dr. Swaminath reports receiving advanced IBD fellowship support from Janssen and Takeda and is on the advisory board for Boehringer Ingelheim.

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

Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.

Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.

“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.

Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.

“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
 

Old concept enhancing current practice

The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.

“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.

What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.

AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
 

AI systems in IBD – do they work?

Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.

The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.

“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.

Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
 

Simplifying histological scoring

Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.

“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”

Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.

The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.

“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
 

Assessing the gut in real time

Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.

“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.

“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.

The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.

“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.

The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.

The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.

Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.

Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.

“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.

Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.

“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
 

Old concept enhancing current practice

The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.

“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.

What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.

AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
 

AI systems in IBD – do they work?

Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.

The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.

“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.

Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
 

Simplifying histological scoring

Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.

“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”

Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.

The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.

“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
 

Assessing the gut in real time

Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.

“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.

“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.

The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.

“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.

The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.

The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.

Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.

Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.

“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.

Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.

“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
 

Old concept enhancing current practice

The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.

“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.

What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.

AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
 

AI systems in IBD – do they work?

Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.

The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.

“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.

Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
 

Simplifying histological scoring

Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.

“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”

Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.

The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.

“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
 

Assessing the gut in real time

Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.

“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.

“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.

The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.

“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.

The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.

The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.

The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).

“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.

“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.

“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.

“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.

“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.

“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
 

VTE risk in IBD patients

The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”

Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.

The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
 

Large hospitalized IBD population considered

Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.

“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.

All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.

A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.

With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”

Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.

Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
 

Ideal thromboprophylaxis duration under investigation

“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.

“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.

The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.

“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.

Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
 

The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.

The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).

“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.

“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.

“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.

“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.

“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.

“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
 

VTE risk in IBD patients

The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”

Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.

The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
 

Large hospitalized IBD population considered

Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.

“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.

All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.

A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.

With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”

Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.

Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
 

Ideal thromboprophylaxis duration under investigation

“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.

“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.

The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.

“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.

Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
 

The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.

The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).

“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.

“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.

“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.

“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.

“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.

“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
 

VTE risk in IBD patients

The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”

Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.

The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
 

Large hospitalized IBD population considered

Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.

“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.

All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.

A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.

With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”

Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.

Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
 

Ideal thromboprophylaxis duration under investigation

“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.

“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.

The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.

“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.

Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
 

A new study examining avoidant/restrictive food intake disorder (ARFID) among patients with celiac disease found that the condition is common but is not associated with any difference in disease control. The findings suggest that some with celiac disease may pursue dietary control too far, but experts warn that ARFID is only recently being recognized in patients with GI diseases, the definition is in flux, and it’s important to not overpathologize patient behavior.

The new study, published in Gastro Hep Advances, comes in the wake of a 2021 cross-sectional study, which found that 53.7% of celiac disease patients met the criteria for ARFID based on the Nine-Item ARFID Screen, and were more likely to have anxiety, depression, and reduced food-related quality of life.

chameleonseye/Thinkstock

“I think both studies are hypothesizing that there might be greater fear around eating in these patients with celiac, but that the possible outcomes related to their disease may not actually be different,” said Helen Burton Murray, PhD, director of the GI behavioral health program and staff psychologist at Massachusetts General Hospital, Boston, who was asked to comment on the study.

She also noted that ARFID may represent a subgroup of celiac patients with more severe disease or worse quality of life, though the two studies can’t definitively prove that. The surveys used are intended for screening rather than diagnosis and have not yet been validated in patients with a gastrointestinal disease like celiac.

Although the symptoms of ARFID have been recognized for many years, it only became an official diagnosis with its inclusion in DSM-5 in 2013. Physicians are becoming increasingly aware of this potential comorbidity, but it can be difficult to diagnose or understand the impact of an eating disorder in a condition like celiac disease, where intense dietary management is the key to controlling it. “There’s concern about overpathologizing patients where dietary management can be a normative strategy, and overpathologizing by diagnosing ARFID. Is diagnosing ARFID going to change the patient’s treatment course and improve outcomes for them?” asked Dr. Burton Murray.

In some cases, the answer may be yes. Patients may be so restrictive in their eating that it impacts physical health or lifestyle. “Hypervigilance or worry around eating could extend to even non–gluten based foods. That may be a marker of where a patient’s eating behaviors are crossing the line into ARFID, if their diet is so limited when it doesn’t need to be, and those limitations might be harming them nutritionally, leading to weight loss or making it difficult to live their life in the way that they would like to,” said Dr. Burton Murray.

Still, the results of these studies shouldn’t be overinterpreted, according to Anne R. Lee, EdD, RDN, LD, associate professor of nutritional medicine at the celiac disease center at Columbia University, New York. “In the world of eating disorders, ARFID is the newest kid on the block, and one that’s in transition,” she said. What differentiates ARFID from other eating disorders is that food behavior is related to things like appetite or picky eating, but not body shape and size. Therefore, it helps to combine the ARFID screen with other eating disorder screening tools, Dr. Lee said.

“We need to differentiate between diagnosing someone with a disordered eating pattern versus helping them navigate their life within a gluten-free diet. We need to help them with developing strategies to maneuver through work lunches and social outings and all of those things so that we don’t overdiagnose,” said Dr. Lee.

In the new study, researchers retrospectively analyzed data from 137 patients with celiac disease at the Center for Human Nutrition at Vanderbilt University Medical Center; 107 were women, and the median age was 37 years. The researchers used questionnaires to evaluate diet, including the ARFID Symptom Checklist.

Seventy-eight participants (57%) had suspected ARFID; 30 had symptoms consistent with clinical ARFID and 48 consistent with subclinical ARFID. There were no differences between patients with and without ARFID with respect to anxiety and depression, length of illness, age, gender, body mass index, bone disease, or micronutrient or vitamin deficiency. Serology studies revealed only one difference: a higher frequency of tissue transglutaminase IgG antibody in the ARFID group (15% vs. 2%; P = .007).

There was a strong correlation between ARFID and the Impact of the Gluten Free Diet questionnaire (IGFDQ), with patients scoring higher on the social and food components more likely to also have ARFID. It was also the only predictor of ARFID in a multivariable analysis, with associations in the food (odds ratio, 1.64; P = .01), emotional (OR, 1.66; P = .05), and social (OR, 1.59; P = .01) sections.

The authors concluded that, although there were some study limitations, including possible patient misunderstanding of the survey questions and lack of knowledge of whether the patients had access to gluten-free foods, AFID is not only common, but it also has a significant impact on patients with celiac disease. The authors also noted that this assessment occurred over a 2-year period, with patients attending clinic only once a year. Follow-up surveys, duodenal biopsies, and bone density assessments could identify more differences over time.

Dr. Burton Murray and Dr. Lee have no relevant financial disclosures.

AGA offers guidance on celiac disease to help patients maintain a gluten free diet in the AGA GI Patient Center: www.gastro.org/celiac

A new study examining avoidant/restrictive food intake disorder (ARFID) among patients with celiac disease found that the condition is common but is not associated with any difference in disease control. The findings suggest that some with celiac disease may pursue dietary control too far, but experts warn that ARFID is only recently being recognized in patients with GI diseases, the definition is in flux, and it’s important to not overpathologize patient behavior.

The new study, published in Gastro Hep Advances, comes in the wake of a 2021 cross-sectional study, which found that 53.7% of celiac disease patients met the criteria for ARFID based on the Nine-Item ARFID Screen, and were more likely to have anxiety, depression, and reduced food-related quality of life.

chameleonseye/Thinkstock

“I think both studies are hypothesizing that there might be greater fear around eating in these patients with celiac, but that the possible outcomes related to their disease may not actually be different,” said Helen Burton Murray, PhD, director of the GI behavioral health program and staff psychologist at Massachusetts General Hospital, Boston, who was asked to comment on the study.

She also noted that ARFID may represent a subgroup of celiac patients with more severe disease or worse quality of life, though the two studies can’t definitively prove that. The surveys used are intended for screening rather than diagnosis and have not yet been validated in patients with a gastrointestinal disease like celiac.

Although the symptoms of ARFID have been recognized for many years, it only became an official diagnosis with its inclusion in DSM-5 in 2013. Physicians are becoming increasingly aware of this potential comorbidity, but it can be difficult to diagnose or understand the impact of an eating disorder in a condition like celiac disease, where intense dietary management is the key to controlling it. “There’s concern about overpathologizing patients where dietary management can be a normative strategy, and overpathologizing by diagnosing ARFID. Is diagnosing ARFID going to change the patient’s treatment course and improve outcomes for them?” asked Dr. Burton Murray.

In some cases, the answer may be yes. Patients may be so restrictive in their eating that it impacts physical health or lifestyle. “Hypervigilance or worry around eating could extend to even non–gluten based foods. That may be a marker of where a patient’s eating behaviors are crossing the line into ARFID, if their diet is so limited when it doesn’t need to be, and those limitations might be harming them nutritionally, leading to weight loss or making it difficult to live their life in the way that they would like to,” said Dr. Burton Murray.

Still, the results of these studies shouldn’t be overinterpreted, according to Anne R. Lee, EdD, RDN, LD, associate professor of nutritional medicine at the celiac disease center at Columbia University, New York. “In the world of eating disorders, ARFID is the newest kid on the block, and one that’s in transition,” she said. What differentiates ARFID from other eating disorders is that food behavior is related to things like appetite or picky eating, but not body shape and size. Therefore, it helps to combine the ARFID screen with other eating disorder screening tools, Dr. Lee said.

“We need to differentiate between diagnosing someone with a disordered eating pattern versus helping them navigate their life within a gluten-free diet. We need to help them with developing strategies to maneuver through work lunches and social outings and all of those things so that we don’t overdiagnose,” said Dr. Lee.

In the new study, researchers retrospectively analyzed data from 137 patients with celiac disease at the Center for Human Nutrition at Vanderbilt University Medical Center; 107 were women, and the median age was 37 years. The researchers used questionnaires to evaluate diet, including the ARFID Symptom Checklist.

Seventy-eight participants (57%) had suspected ARFID; 30 had symptoms consistent with clinical ARFID and 48 consistent with subclinical ARFID. There were no differences between patients with and without ARFID with respect to anxiety and depression, length of illness, age, gender, body mass index, bone disease, or micronutrient or vitamin deficiency. Serology studies revealed only one difference: a higher frequency of tissue transglutaminase IgG antibody in the ARFID group (15% vs. 2%; P = .007).

There was a strong correlation between ARFID and the Impact of the Gluten Free Diet questionnaire (IGFDQ), with patients scoring higher on the social and food components more likely to also have ARFID. It was also the only predictor of ARFID in a multivariable analysis, with associations in the food (odds ratio, 1.64; P = .01), emotional (OR, 1.66; P = .05), and social (OR, 1.59; P = .01) sections.

The authors concluded that, although there were some study limitations, including possible patient misunderstanding of the survey questions and lack of knowledge of whether the patients had access to gluten-free foods, AFID is not only common, but it also has a significant impact on patients with celiac disease. The authors also noted that this assessment occurred over a 2-year period, with patients attending clinic only once a year. Follow-up surveys, duodenal biopsies, and bone density assessments could identify more differences over time.

Dr. Burton Murray and Dr. Lee have no relevant financial disclosures.

AGA offers guidance on celiac disease to help patients maintain a gluten free diet in the AGA GI Patient Center: www.gastro.org/celiac

A new study examining avoidant/restrictive food intake disorder (ARFID) among patients with celiac disease found that the condition is common but is not associated with any difference in disease control. The findings suggest that some with celiac disease may pursue dietary control too far, but experts warn that ARFID is only recently being recognized in patients with GI diseases, the definition is in flux, and it’s important to not overpathologize patient behavior.

The new study, published in Gastro Hep Advances, comes in the wake of a 2021 cross-sectional study, which found that 53.7% of celiac disease patients met the criteria for ARFID based on the Nine-Item ARFID Screen, and were more likely to have anxiety, depression, and reduced food-related quality of life.

chameleonseye/Thinkstock

“I think both studies are hypothesizing that there might be greater fear around eating in these patients with celiac, but that the possible outcomes related to their disease may not actually be different,” said Helen Burton Murray, PhD, director of the GI behavioral health program and staff psychologist at Massachusetts General Hospital, Boston, who was asked to comment on the study.

She also noted that ARFID may represent a subgroup of celiac patients with more severe disease or worse quality of life, though the two studies can’t definitively prove that. The surveys used are intended for screening rather than diagnosis and have not yet been validated in patients with a gastrointestinal disease like celiac.

Although the symptoms of ARFID have been recognized for many years, it only became an official diagnosis with its inclusion in DSM-5 in 2013. Physicians are becoming increasingly aware of this potential comorbidity, but it can be difficult to diagnose or understand the impact of an eating disorder in a condition like celiac disease, where intense dietary management is the key to controlling it. “There’s concern about overpathologizing patients where dietary management can be a normative strategy, and overpathologizing by diagnosing ARFID. Is diagnosing ARFID going to change the patient’s treatment course and improve outcomes for them?” asked Dr. Burton Murray.

In some cases, the answer may be yes. Patients may be so restrictive in their eating that it impacts physical health or lifestyle. “Hypervigilance or worry around eating could extend to even non–gluten based foods. That may be a marker of where a patient’s eating behaviors are crossing the line into ARFID, if their diet is so limited when it doesn’t need to be, and those limitations might be harming them nutritionally, leading to weight loss or making it difficult to live their life in the way that they would like to,” said Dr. Burton Murray.

Still, the results of these studies shouldn’t be overinterpreted, according to Anne R. Lee, EdD, RDN, LD, associate professor of nutritional medicine at the celiac disease center at Columbia University, New York. “In the world of eating disorders, ARFID is the newest kid on the block, and one that’s in transition,” she said. What differentiates ARFID from other eating disorders is that food behavior is related to things like appetite or picky eating, but not body shape and size. Therefore, it helps to combine the ARFID screen with other eating disorder screening tools, Dr. Lee said.

“We need to differentiate between diagnosing someone with a disordered eating pattern versus helping them navigate their life within a gluten-free diet. We need to help them with developing strategies to maneuver through work lunches and social outings and all of those things so that we don’t overdiagnose,” said Dr. Lee.

In the new study, researchers retrospectively analyzed data from 137 patients with celiac disease at the Center for Human Nutrition at Vanderbilt University Medical Center; 107 were women, and the median age was 37 years. The researchers used questionnaires to evaluate diet, including the ARFID Symptom Checklist.

Seventy-eight participants (57%) had suspected ARFID; 30 had symptoms consistent with clinical ARFID and 48 consistent with subclinical ARFID. There were no differences between patients with and without ARFID with respect to anxiety and depression, length of illness, age, gender, body mass index, bone disease, or micronutrient or vitamin deficiency. Serology studies revealed only one difference: a higher frequency of tissue transglutaminase IgG antibody in the ARFID group (15% vs. 2%; P = .007).

There was a strong correlation between ARFID and the Impact of the Gluten Free Diet questionnaire (IGFDQ), with patients scoring higher on the social and food components more likely to also have ARFID. It was also the only predictor of ARFID in a multivariable analysis, with associations in the food (odds ratio, 1.64; P = .01), emotional (OR, 1.66; P = .05), and social (OR, 1.59; P = .01) sections.

The authors concluded that, although there were some study limitations, including possible patient misunderstanding of the survey questions and lack of knowledge of whether the patients had access to gluten-free foods, AFID is not only common, but it also has a significant impact on patients with celiac disease. The authors also noted that this assessment occurred over a 2-year period, with patients attending clinic only once a year. Follow-up surveys, duodenal biopsies, and bone density assessments could identify more differences over time.

Dr. Burton Murray and Dr. Lee have no relevant financial disclosures.

AGA offers guidance on celiac disease to help patients maintain a gluten free diet in the AGA GI Patient Center: www.gastro.org/celiac

Mirikizumab is the first interleukin (IL) 23p19 to report positive phase 3 results for induction therapy in patients who have moderate to severe ulcerative colitis (UC) and have already been treated with at least one prior therapy.

Compared to placebo, almost a quarter (24.2%) of patients treated with mirikizumab versus 13% of those treated with placebo were in clinical remission at the end of the 12-week LUCENT-1 study. This was the study’s primary endpoint and it was a significant result (P = .00006), study investigator Geert D’Haens, MD, PhD, reported at the 17th congress of the European Crohn’s and Colitis Organisation.

Moreover, mirikizumab met all its secondary endpoints in the trial. At the end of the study almost two-thirds (63.5%) of patients achieved a clinical response (vs. 42.2% in the placebo arm); over one-third (36.3%) exhibited endoscopic remission (vs. 21.1%), and just over a quarter (27.1% vs. 13.9%) showed histologic-endoscopic mucosal improvement, according to a press release. The P values for all comparisons were less than .00001.

Perhaps more importantly from the patient perspective, there was greater symptomatic improvement and less bowel urgency in those treated with mirikizumab versus those randomized to placebo.

“The results confirmed [the] efficacy and safety noted in the phase 2 induction [trials], and supports mirikizumab’s potential as treatment for ulcerative colitis,” said Dr. D’Haens, professor of gastroenterology and hepatology at Amsterdam University Medical Centers.

Dominik Bettenworth, MD, who was not involved in the study, said that “the positive results from the LUCENT-1 trial are an important step towards selective IL-23 inhibition as a new mode of action for the treatment of patients with UC.

“This treatment approach has been shown efficacious and launched in other immune-mediated diseases such as psoriasis,” said Dr. Bettenworth, a specialist in internal medicine and gastroenterology in Münster, Germany.

“Noteworthy, for the first time in a phase 3 trial in IBD, [bowel] urgency has been assessed as a secondary endpoint – a clinical symptom of particular importance for patients with UC,” he added, noting that regarding safety, “the LUCENT-1 trial further confirms the previously observed overall good safety profile of IL-23 inhibitors.”
 

About mirikizumab and LUCENT-1

Mirikizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and is one of several IL23p19 antibodies currently under investigation for the treatment of IBD.

LUCENT-1 was a multicenter, randomized, double-blind, parallel group, placebo-controlled induction study in just over 1,200 patients aged 18-80 years. For inclusion, patients had to have moderately to severely active UC and had to have received at least one prior therapy, but had an inadequate or loss of response to it or been intolerant of it. Baseline data showed that 40% of patients included had been treated with corticosteroids and 24% with immunomodulators, and any current treatment remained unchanged during the study. Biologic treatment had failed in about 40% of patients and any patient taking such therapy had to discontinue it before participating in the trial.

Patients were randomized to receive 300 mg of mirikizumab or matching placebo, given intravenously at weeks 0, 4, and 8. Dr. D’Haens noted that randomization had been in a 3:1 ratio and had been stratified according to various factors such as biologic failure status, corticosteroid use, baseline disease activity, and region of the world where the patient was recruited.
 

Better results if biologic naive

Clinical remission was stringently defined as: Mayo stool frequency subscore of zero or one, with a reduction of one point or greater from baseline; no rectal bleeding; and a Mayo endoscopic subscore of zero to one. When looking at this primary endpoint in terms of whether patients had received prior biologic treatment, there was a higher remission rate at week 12 if patients had not previously been given any biologic therapy than if they had, but rates were still higher than placebo (30.9% vs. 15.8% and 15.2% vs. 8.5%, respectively), according to the press release. The P value was less than .001 for both comparisons although the study was not powered to look at these subgroups of patients.

Similarly, for clinical response – which was a decrease in the modified Mayo score of 2 or more points and at least a 30% decrease from initial values, as well as a decrease in rectal bleeding – there were differences between patients who had (54.6% for mirikizumab vs. 29.7% for placebo) and had not (70.1% vs. 50.3%) received a biologic previously (again, P less than .001 for both comparisons).

“Control of bowel function is one of the most debilitating, or one of the most important features for patients with ulcerative colitis,” Dr. D’Haens said when presenting the data on bowel urgency. In the trial there was an improvement in urgency – which was rated by patients – starting as early as week 2, with further improvement seen as the induction period went on.
 

Mirikizumab safety consistent with other trials

Dr. D’Haens noted that the safety profile of IL23 antibodies was “extremely clean.” As with other trials of mirikizumab, he said, there were similar or lower rates to placebo for many adverse events including any infection (15.1% vs. 14%) and cerebrocardiovascular events (0.6% vs. 0.1%). The overall rate of treatment emergent adverse events was 44.5% vs. 46.1% for mirikizumab and placebo. Notably, there were fewer serious adverse events (2.8% vs. 5.3%.) and discontinuations because of side effects (1.6% vs. 7.2%) in the mirikizumab group.

Are gastroenterologists now spoiled for choice?

Lots of questions followed Dr. D’Haens presentation, many picking up on the high placebo response and remission rates.

“We’ve seen it in a number of trials now,” Dr. D’Haens said. “One of the reasons is that patients are allowed to start corticosteroids as late as 2 weeks before randomization,” he observed. In LUCENT-1, half of the patients that were using steroids were receiving a dose of 20 mg of prednisone.

“Now when you start 20 mg of prednisone 2 weeks before randomization that might have an impact on your placebo readout. So I think that’s a lesson for many more trials in the future,” Dr. D’Haens said,”

A high placebo response rate was not expected and another hypothesis is that maybe additional clinical support for fatigue that was received may have played a role.

Several delegates asked for guidance on where mirikizumab and other IL-23p19 blockers might now fit in the grand scheme of patient treatment.

“It is really nice to have expanding therapeutic options but how will we choose?” said one in the online Q&A. “Which IL23 antagonist should we be using now?” and “Is ustekinumab obsolete in UC?” asked others.

“I think it’s early days to decide where the field is going,” Dr. D’Haens said after his presentation. “We don’t have head-to-head data. In GALAXI, ustekinumab was a reference arm.”

There will be further subanalyses of LUCENT-1 to come, including results from endoscopy and histology investigations, and the maintenance trial LUCENT-2 will also report soon.

“The feeling is that IL23 blockade is more specific, [more] beneficial in inflammatory bowel disease than blocking both IL12 and IL23,” Dr. D’Haens said.

Dr. D’Haens was an investigator in the LUCENT-1 trial and has acted as an adviser to the study’s sponsor, Eli Lilly, among many other big pharma companies. Dr. Bettenworth is on the advisory board or is a consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Else Kröner-Fresenius-Foundation, Galapagos, Guidepoint, Impulze, Falk Foundation, Ferring, Janssen Cilag, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, and Vifor Pharma.

Mirikizumab is the first interleukin (IL) 23p19 to report positive phase 3 results for induction therapy in patients who have moderate to severe ulcerative colitis (UC) and have already been treated with at least one prior therapy.

Compared to placebo, almost a quarter (24.2%) of patients treated with mirikizumab versus 13% of those treated with placebo were in clinical remission at the end of the 12-week LUCENT-1 study. This was the study’s primary endpoint and it was a significant result (P = .00006), study investigator Geert D’Haens, MD, PhD, reported at the 17th congress of the European Crohn’s and Colitis Organisation.

Moreover, mirikizumab met all its secondary endpoints in the trial. At the end of the study almost two-thirds (63.5%) of patients achieved a clinical response (vs. 42.2% in the placebo arm); over one-third (36.3%) exhibited endoscopic remission (vs. 21.1%), and just over a quarter (27.1% vs. 13.9%) showed histologic-endoscopic mucosal improvement, according to a press release. The P values for all comparisons were less than .00001.

Perhaps more importantly from the patient perspective, there was greater symptomatic improvement and less bowel urgency in those treated with mirikizumab versus those randomized to placebo.

“The results confirmed [the] efficacy and safety noted in the phase 2 induction [trials], and supports mirikizumab’s potential as treatment for ulcerative colitis,” said Dr. D’Haens, professor of gastroenterology and hepatology at Amsterdam University Medical Centers.

Dominik Bettenworth, MD, who was not involved in the study, said that “the positive results from the LUCENT-1 trial are an important step towards selective IL-23 inhibition as a new mode of action for the treatment of patients with UC.

“This treatment approach has been shown efficacious and launched in other immune-mediated diseases such as psoriasis,” said Dr. Bettenworth, a specialist in internal medicine and gastroenterology in Münster, Germany.

“Noteworthy, for the first time in a phase 3 trial in IBD, [bowel] urgency has been assessed as a secondary endpoint – a clinical symptom of particular importance for patients with UC,” he added, noting that regarding safety, “the LUCENT-1 trial further confirms the previously observed overall good safety profile of IL-23 inhibitors.”
 

About mirikizumab and LUCENT-1

Mirikizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and is one of several IL23p19 antibodies currently under investigation for the treatment of IBD.

LUCENT-1 was a multicenter, randomized, double-blind, parallel group, placebo-controlled induction study in just over 1,200 patients aged 18-80 years. For inclusion, patients had to have moderately to severely active UC and had to have received at least one prior therapy, but had an inadequate or loss of response to it or been intolerant of it. Baseline data showed that 40% of patients included had been treated with corticosteroids and 24% with immunomodulators, and any current treatment remained unchanged during the study. Biologic treatment had failed in about 40% of patients and any patient taking such therapy had to discontinue it before participating in the trial.

Patients were randomized to receive 300 mg of mirikizumab or matching placebo, given intravenously at weeks 0, 4, and 8. Dr. D’Haens noted that randomization had been in a 3:1 ratio and had been stratified according to various factors such as biologic failure status, corticosteroid use, baseline disease activity, and region of the world where the patient was recruited.
 

Better results if biologic naive

Clinical remission was stringently defined as: Mayo stool frequency subscore of zero or one, with a reduction of one point or greater from baseline; no rectal bleeding; and a Mayo endoscopic subscore of zero to one. When looking at this primary endpoint in terms of whether patients had received prior biologic treatment, there was a higher remission rate at week 12 if patients had not previously been given any biologic therapy than if they had, but rates were still higher than placebo (30.9% vs. 15.8% and 15.2% vs. 8.5%, respectively), according to the press release. The P value was less than .001 for both comparisons although the study was not powered to look at these subgroups of patients.

Similarly, for clinical response – which was a decrease in the modified Mayo score of 2 or more points and at least a 30% decrease from initial values, as well as a decrease in rectal bleeding – there were differences between patients who had (54.6% for mirikizumab vs. 29.7% for placebo) and had not (70.1% vs. 50.3%) received a biologic previously (again, P less than .001 for both comparisons).

“Control of bowel function is one of the most debilitating, or one of the most important features for patients with ulcerative colitis,” Dr. D’Haens said when presenting the data on bowel urgency. In the trial there was an improvement in urgency – which was rated by patients – starting as early as week 2, with further improvement seen as the induction period went on.
 

Mirikizumab safety consistent with other trials

Dr. D’Haens noted that the safety profile of IL23 antibodies was “extremely clean.” As with other trials of mirikizumab, he said, there were similar or lower rates to placebo for many adverse events including any infection (15.1% vs. 14%) and cerebrocardiovascular events (0.6% vs. 0.1%). The overall rate of treatment emergent adverse events was 44.5% vs. 46.1% for mirikizumab and placebo. Notably, there were fewer serious adverse events (2.8% vs. 5.3%.) and discontinuations because of side effects (1.6% vs. 7.2%) in the mirikizumab group.

Are gastroenterologists now spoiled for choice?

Lots of questions followed Dr. D’Haens presentation, many picking up on the high placebo response and remission rates.

“We’ve seen it in a number of trials now,” Dr. D’Haens said. “One of the reasons is that patients are allowed to start corticosteroids as late as 2 weeks before randomization,” he observed. In LUCENT-1, half of the patients that were using steroids were receiving a dose of 20 mg of prednisone.

“Now when you start 20 mg of prednisone 2 weeks before randomization that might have an impact on your placebo readout. So I think that’s a lesson for many more trials in the future,” Dr. D’Haens said,”

A high placebo response rate was not expected and another hypothesis is that maybe additional clinical support for fatigue that was received may have played a role.

Several delegates asked for guidance on where mirikizumab and other IL-23p19 blockers might now fit in the grand scheme of patient treatment.

“It is really nice to have expanding therapeutic options but how will we choose?” said one in the online Q&A. “Which IL23 antagonist should we be using now?” and “Is ustekinumab obsolete in UC?” asked others.

“I think it’s early days to decide where the field is going,” Dr. D’Haens said after his presentation. “We don’t have head-to-head data. In GALAXI, ustekinumab was a reference arm.”

There will be further subanalyses of LUCENT-1 to come, including results from endoscopy and histology investigations, and the maintenance trial LUCENT-2 will also report soon.

“The feeling is that IL23 blockade is more specific, [more] beneficial in inflammatory bowel disease than blocking both IL12 and IL23,” Dr. D’Haens said.

Dr. D’Haens was an investigator in the LUCENT-1 trial and has acted as an adviser to the study’s sponsor, Eli Lilly, among many other big pharma companies. Dr. Bettenworth is on the advisory board or is a consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Else Kröner-Fresenius-Foundation, Galapagos, Guidepoint, Impulze, Falk Foundation, Ferring, Janssen Cilag, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, and Vifor Pharma.

Mirikizumab is the first interleukin (IL) 23p19 to report positive phase 3 results for induction therapy in patients who have moderate to severe ulcerative colitis (UC) and have already been treated with at least one prior therapy.

Compared to placebo, almost a quarter (24.2%) of patients treated with mirikizumab versus 13% of those treated with placebo were in clinical remission at the end of the 12-week LUCENT-1 study. This was the study’s primary endpoint and it was a significant result (P = .00006), study investigator Geert D’Haens, MD, PhD, reported at the 17th congress of the European Crohn’s and Colitis Organisation.

Moreover, mirikizumab met all its secondary endpoints in the trial. At the end of the study almost two-thirds (63.5%) of patients achieved a clinical response (vs. 42.2% in the placebo arm); over one-third (36.3%) exhibited endoscopic remission (vs. 21.1%), and just over a quarter (27.1% vs. 13.9%) showed histologic-endoscopic mucosal improvement, according to a press release. The P values for all comparisons were less than .00001.

Perhaps more importantly from the patient perspective, there was greater symptomatic improvement and less bowel urgency in those treated with mirikizumab versus those randomized to placebo.

“The results confirmed [the] efficacy and safety noted in the phase 2 induction [trials], and supports mirikizumab’s potential as treatment for ulcerative colitis,” said Dr. D’Haens, professor of gastroenterology and hepatology at Amsterdam University Medical Centers.

Dominik Bettenworth, MD, who was not involved in the study, said that “the positive results from the LUCENT-1 trial are an important step towards selective IL-23 inhibition as a new mode of action for the treatment of patients with UC.

“This treatment approach has been shown efficacious and launched in other immune-mediated diseases such as psoriasis,” said Dr. Bettenworth, a specialist in internal medicine and gastroenterology in Münster, Germany.

“Noteworthy, for the first time in a phase 3 trial in IBD, [bowel] urgency has been assessed as a secondary endpoint – a clinical symptom of particular importance for patients with UC,” he added, noting that regarding safety, “the LUCENT-1 trial further confirms the previously observed overall good safety profile of IL-23 inhibitors.”
 

About mirikizumab and LUCENT-1

Mirikizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and is one of several IL23p19 antibodies currently under investigation for the treatment of IBD.

LUCENT-1 was a multicenter, randomized, double-blind, parallel group, placebo-controlled induction study in just over 1,200 patients aged 18-80 years. For inclusion, patients had to have moderately to severely active UC and had to have received at least one prior therapy, but had an inadequate or loss of response to it or been intolerant of it. Baseline data showed that 40% of patients included had been treated with corticosteroids and 24% with immunomodulators, and any current treatment remained unchanged during the study. Biologic treatment had failed in about 40% of patients and any patient taking such therapy had to discontinue it before participating in the trial.

Patients were randomized to receive 300 mg of mirikizumab or matching placebo, given intravenously at weeks 0, 4, and 8. Dr. D’Haens noted that randomization had been in a 3:1 ratio and had been stratified according to various factors such as biologic failure status, corticosteroid use, baseline disease activity, and region of the world where the patient was recruited.
 

Better results if biologic naive

Clinical remission was stringently defined as: Mayo stool frequency subscore of zero or one, with a reduction of one point or greater from baseline; no rectal bleeding; and a Mayo endoscopic subscore of zero to one. When looking at this primary endpoint in terms of whether patients had received prior biologic treatment, there was a higher remission rate at week 12 if patients had not previously been given any biologic therapy than if they had, but rates were still higher than placebo (30.9% vs. 15.8% and 15.2% vs. 8.5%, respectively), according to the press release. The P value was less than .001 for both comparisons although the study was not powered to look at these subgroups of patients.

Similarly, for clinical response – which was a decrease in the modified Mayo score of 2 or more points and at least a 30% decrease from initial values, as well as a decrease in rectal bleeding – there were differences between patients who had (54.6% for mirikizumab vs. 29.7% for placebo) and had not (70.1% vs. 50.3%) received a biologic previously (again, P less than .001 for both comparisons).

“Control of bowel function is one of the most debilitating, or one of the most important features for patients with ulcerative colitis,” Dr. D’Haens said when presenting the data on bowel urgency. In the trial there was an improvement in urgency – which was rated by patients – starting as early as week 2, with further improvement seen as the induction period went on.
 

Mirikizumab safety consistent with other trials

Dr. D’Haens noted that the safety profile of IL23 antibodies was “extremely clean.” As with other trials of mirikizumab, he said, there were similar or lower rates to placebo for many adverse events including any infection (15.1% vs. 14%) and cerebrocardiovascular events (0.6% vs. 0.1%). The overall rate of treatment emergent adverse events was 44.5% vs. 46.1% for mirikizumab and placebo. Notably, there were fewer serious adverse events (2.8% vs. 5.3%.) and discontinuations because of side effects (1.6% vs. 7.2%) in the mirikizumab group.

Are gastroenterologists now spoiled for choice?

Lots of questions followed Dr. D’Haens presentation, many picking up on the high placebo response and remission rates.

“We’ve seen it in a number of trials now,” Dr. D’Haens said. “One of the reasons is that patients are allowed to start corticosteroids as late as 2 weeks before randomization,” he observed. In LUCENT-1, half of the patients that were using steroids were receiving a dose of 20 mg of prednisone.

“Now when you start 20 mg of prednisone 2 weeks before randomization that might have an impact on your placebo readout. So I think that’s a lesson for many more trials in the future,” Dr. D’Haens said,”

A high placebo response rate was not expected and another hypothesis is that maybe additional clinical support for fatigue that was received may have played a role.

Several delegates asked for guidance on where mirikizumab and other IL-23p19 blockers might now fit in the grand scheme of patient treatment.

“It is really nice to have expanding therapeutic options but how will we choose?” said one in the online Q&A. “Which IL23 antagonist should we be using now?” and “Is ustekinumab obsolete in UC?” asked others.

“I think it’s early days to decide where the field is going,” Dr. D’Haens said after his presentation. “We don’t have head-to-head data. In GALAXI, ustekinumab was a reference arm.”

There will be further subanalyses of LUCENT-1 to come, including results from endoscopy and histology investigations, and the maintenance trial LUCENT-2 will also report soon.

“The feeling is that IL23 blockade is more specific, [more] beneficial in inflammatory bowel disease than blocking both IL12 and IL23,” Dr. D’Haens said.

Dr. D’Haens was an investigator in the LUCENT-1 trial and has acted as an adviser to the study’s sponsor, Eli Lilly, among many other big pharma companies. Dr. Bettenworth is on the advisory board or is a consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Else Kröner-Fresenius-Foundation, Galapagos, Guidepoint, Impulze, Falk Foundation, Ferring, Janssen Cilag, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, and Vifor Pharma.