IBD & Intestinal Disorders

Wearable devices like the Apple Watch and Fitbit may help identify and predict inflammatory bowel disease (IBD) flares, and even distinguish between inflammatory and purely symptomatic episodes, according to investigators.

These findings suggest that widely used consumer wearables could support long-term monitoring of IBD and other chronic inflammatory conditions, lead author Robert P. Hirten, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues reported.

 

“Wearable devices are an increasingly accepted tool for monitoring health and disease,” the investigators wrote in Gastroenterology. “They are frequently used in non–inflammatory-based diseases for remote patient monitoring, allowing individuals to be monitored outside of the clinical setting, which has resulted in improved outcomes in multiple disease states.”

Progress has been slower for inflammatory conditions, the investigators noted, despite interest from both providers and patients. Prior studies have explored activity and sleep tracking, or sweat-based biomarkers, as potential tools for monitoring IBD. 

Hirten and colleagues took a novel approach, focusing on physiologic changes driven by autonomic nervous system dysfunction — a hallmark of chronic inflammation. Conditions like IBD are associated with reduced parasympathetic activity and increased sympathetic tone, which in turn affect heart rate and heart rate variability. Heart rate tends to rise during flares, while heart rate variability decreases.

Their prospective cohort study included 309 adults with Crohn’s disease (n = 196) or ulcerative colitis (n = 113). Participants used their own or a study-provided Apple Watch, Fitbit, or Oura Ring to passively collect physiological data, including heart rate, resting heart rate, heart rate variability, and step count. A subset of Apple Watch users also contributed oxygen saturation data.

Participants also completed daily symptom surveys using a custom smartphone app and reported laboratory values such as C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, as part of routine care. These data were used to identify symptomatic and inflammatory flare periods.

Over a mean follow-up of about 7 months, the physiological data consistently distinguished both types of flares from periods of remission. Heart rate variability dropped significantly during flares, while heart rate and resting heart rate increased. Step counts decreased during inflammatory flares but not during symptom-only flares. Oxygen saturation stayed mostly the same, except for a slight drop seen in participants with Crohn’s disease.

These physiological changes could be detected as early as 7 weeks before a flare. Predictive models that combined multiple metrics — heart rate variability, heart rate, resting heart rate, and step count — were highly accurate, with F1 scores as high as 0.90 for predicting inflammatory flares and 0.83 for predicting symptomatic flares.

In addition, wearable data helped differentiate between flares caused by active inflammation and those driven by symptoms alone. Even when symptoms were similar, heart rate variability, heart rate, and resting heart rate were significantly higher when inflammation was present—suggesting wearable devices may help address the common mismatch between symptoms and actual disease activity in IBD.

“These findings support the further evaluation of wearable devices in the monitoring of IBD,” the investigators concluded.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and Ms. Jenny Steingart. The investigators disclosed additional relationships with Agomab, Lilly, Merck, and others.

 

Wearable devices like the Apple Watch and Fitbit may help identify and predict inflammatory bowel disease (IBD) flares, and even distinguish between inflammatory and purely symptomatic episodes, according to investigators.

These findings suggest that widely used consumer wearables could support long-term monitoring of IBD and other chronic inflammatory conditions, lead author Robert P. Hirten, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues reported.

 

“Wearable devices are an increasingly accepted tool for monitoring health and disease,” the investigators wrote in Gastroenterology. “They are frequently used in non–inflammatory-based diseases for remote patient monitoring, allowing individuals to be monitored outside of the clinical setting, which has resulted in improved outcomes in multiple disease states.”

Progress has been slower for inflammatory conditions, the investigators noted, despite interest from both providers and patients. Prior studies have explored activity and sleep tracking, or sweat-based biomarkers, as potential tools for monitoring IBD. 

Hirten and colleagues took a novel approach, focusing on physiologic changes driven by autonomic nervous system dysfunction — a hallmark of chronic inflammation. Conditions like IBD are associated with reduced parasympathetic activity and increased sympathetic tone, which in turn affect heart rate and heart rate variability. Heart rate tends to rise during flares, while heart rate variability decreases.

Their prospective cohort study included 309 adults with Crohn’s disease (n = 196) or ulcerative colitis (n = 113). Participants used their own or a study-provided Apple Watch, Fitbit, or Oura Ring to passively collect physiological data, including heart rate, resting heart rate, heart rate variability, and step count. A subset of Apple Watch users also contributed oxygen saturation data.

Participants also completed daily symptom surveys using a custom smartphone app and reported laboratory values such as C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, as part of routine care. These data were used to identify symptomatic and inflammatory flare periods.

Over a mean follow-up of about 7 months, the physiological data consistently distinguished both types of flares from periods of remission. Heart rate variability dropped significantly during flares, while heart rate and resting heart rate increased. Step counts decreased during inflammatory flares but not during symptom-only flares. Oxygen saturation stayed mostly the same, except for a slight drop seen in participants with Crohn’s disease.

These physiological changes could be detected as early as 7 weeks before a flare. Predictive models that combined multiple metrics — heart rate variability, heart rate, resting heart rate, and step count — were highly accurate, with F1 scores as high as 0.90 for predicting inflammatory flares and 0.83 for predicting symptomatic flares.

In addition, wearable data helped differentiate between flares caused by active inflammation and those driven by symptoms alone. Even when symptoms were similar, heart rate variability, heart rate, and resting heart rate were significantly higher when inflammation was present—suggesting wearable devices may help address the common mismatch between symptoms and actual disease activity in IBD.

“These findings support the further evaluation of wearable devices in the monitoring of IBD,” the investigators concluded.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and Ms. Jenny Steingart. The investigators disclosed additional relationships with Agomab, Lilly, Merck, and others.

 

Wearable devices like the Apple Watch and Fitbit may help identify and predict inflammatory bowel disease (IBD) flares, and even distinguish between inflammatory and purely symptomatic episodes, according to investigators.

These findings suggest that widely used consumer wearables could support long-term monitoring of IBD and other chronic inflammatory conditions, lead author Robert P. Hirten, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues reported.

 

“Wearable devices are an increasingly accepted tool for monitoring health and disease,” the investigators wrote in Gastroenterology. “They are frequently used in non–inflammatory-based diseases for remote patient monitoring, allowing individuals to be monitored outside of the clinical setting, which has resulted in improved outcomes in multiple disease states.”

Progress has been slower for inflammatory conditions, the investigators noted, despite interest from both providers and patients. Prior studies have explored activity and sleep tracking, or sweat-based biomarkers, as potential tools for monitoring IBD. 

Hirten and colleagues took a novel approach, focusing on physiologic changes driven by autonomic nervous system dysfunction — a hallmark of chronic inflammation. Conditions like IBD are associated with reduced parasympathetic activity and increased sympathetic tone, which in turn affect heart rate and heart rate variability. Heart rate tends to rise during flares, while heart rate variability decreases.

Their prospective cohort study included 309 adults with Crohn’s disease (n = 196) or ulcerative colitis (n = 113). Participants used their own or a study-provided Apple Watch, Fitbit, or Oura Ring to passively collect physiological data, including heart rate, resting heart rate, heart rate variability, and step count. A subset of Apple Watch users also contributed oxygen saturation data.

Participants also completed daily symptom surveys using a custom smartphone app and reported laboratory values such as C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, as part of routine care. These data were used to identify symptomatic and inflammatory flare periods.

Over a mean follow-up of about 7 months, the physiological data consistently distinguished both types of flares from periods of remission. Heart rate variability dropped significantly during flares, while heart rate and resting heart rate increased. Step counts decreased during inflammatory flares but not during symptom-only flares. Oxygen saturation stayed mostly the same, except for a slight drop seen in participants with Crohn’s disease.

These physiological changes could be detected as early as 7 weeks before a flare. Predictive models that combined multiple metrics — heart rate variability, heart rate, resting heart rate, and step count — were highly accurate, with F1 scores as high as 0.90 for predicting inflammatory flares and 0.83 for predicting symptomatic flares.

In addition, wearable data helped differentiate between flares caused by active inflammation and those driven by symptoms alone. Even when symptoms were similar, heart rate variability, heart rate, and resting heart rate were significantly higher when inflammation was present—suggesting wearable devices may help address the common mismatch between symptoms and actual disease activity in IBD.

“These findings support the further evaluation of wearable devices in the monitoring of IBD,” the investigators concluded.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and Ms. Jenny Steingart. The investigators disclosed additional relationships with Agomab, Lilly, Merck, and others.

 

WASHINGTON, DC — Age-related neurodegenerative disorders — motor neuron diseases, demyelinating diseases, Alzheimer’s disease, and other proteinopathies — are at an “inflection point,” said researcher Andrea R. Merchak, PhD, with a fuller understanding of disease pathophysiology but an overall dearth of effective disease-modifying treatments.

And this, Merchak said at the Gut Microbiota for Health (GMFH) World Summit 2025, is where the gut microbiome comes in. “The gut-brain axis is important to take into consideration,” she urged, both for gut microbiome researchers — whose collaboration with neurologists and neuroscientists is essential — and for practicing gastroenterologists.

“We are the sum of our environmental exposures,” said Merchak, assistant research professor of neurology at the Indiana University School of Medicine, in Indianapolis. “So for your patient populations, remember you’re not only treating the diseases they’re coming to you with, you’re also treating them for a lifetime of healthy [brain] aging.”

At the center of a healthy aging brain are the brain-residing microglia and peripheral monocytes, she said. These immune cell populations are directly influenced by blood-brain barrier breakdown, inflammation, and gut permeability — and indirectly influenced by microbial products, gastrointestinal (GI) function, and bacterial diversity, Merchak said at the meeting, which was convened by AGA and the European Society of Neurogastroenterology and Motility.

“Many of us grew up learning that the brain is an immune-privileged site, but we’ve been establishing that this is fundamentally not true,” she said. “While the brain does have a privileged status, there are interactions with the blood, with the peripheral immune cells.”

Merchak coauthored a 2024 review in Neurotherapeutics in which she and her colleagues explained that the brain is “heavily connected with peripheral immune dynamics,” and that the gut — as the largest immune organ in the body — is a critical place for peripheral immune development, “thus influencing brain health.”

Gut microbiota interact with the brain via several mechanisms including microbiota-derived metabolites that enter circulation, direct communication via the vagus nerve, and modulation of the immune system, Merchak and her coauthors wrote. Leaky gut, they noted, can lead to an accumulation of inflammatory signals and cells that can exacerbate or induce the onset of neurodegenerative conditions.

As researchers better understand the role that GI dysfunction plays in neurodegenerative disease — as they identify microbiome signatures for predicting risk, for instance — there will be “opportunities to target the microbiome to prevent or reverse dysbiosis as a way to delay, arrest or prevent the onset and progression of neurodegenerative diseases,” they wrote.

At the GMFH meeting, Merchak described both ongoing preclinical research that is dissecting gut-brain communication, and preliminary clinical evidence for the use of gut microbiota-modulating therapies in neurodegenerative disease.

 

Support for a Gut-Focused Approach

Research on bile acid metabolism in multiple sclerosis (MS) and on peripheral inflammation in dementia exemplify the ongoing preclinical research uncovering the mechanisms of gut-brain communication, Merchak said.

The finding that bile acid metabolism modulates MS autoimmunity comes from research done by Merchak and a team at the University of Virginia, Charlottesville, Virginia, several years ago in which mice with experimental autoimmune encephalomyelitis (EAE) — an animal model of MS — were engineered for T cell specific knockout of the aryl hydrocarbon receptor (AHR). The AHR has been directly tied to MS, and T lymphocytes are known to play a central role in MS pathophysiology.

Blocking the activity of AHR in CD4-positive T cells significantly affected the production of bile acids and other metabolites in the microbiome — and the outcome of central nervous system autoimmunity. “Mice with high levels of bile acids, both primary and secondary, actually recovered from this EAE” and regained motor function, Merchak said at the GMFH meeting.

The potential impact of genetic manipulation on recovery was ruled out — and the role of bile acids confirmed — when, using the EAE model, gut bacteria from mice without AHR were transplanted into mice with AHR. The mice with AHR were able to recover, confirming that AHR can reprogram the gut microbiome and that “high levels of bile acid can lead to reduced autoimmunity in an MS model,” she said.

Other elements and stages of the research, which was published in PLOS Biology in 2023, showed increased apoptosis of CD4-positive immune cells in AHR-deficient mice and the ability of oral taurocholic acid — a bile acid that was especially high in mice without AHR — to reduce the severity of EAE, Merchak said.

Evidence for the role of gut and peripheral inflammation on neurodegeneration is building on numerous fronts, Merchak said. Unpublished research using spatial transcriptomics of colon biopsies from patients with inflammatory bowel disease (IBD), patients with Parkinson’s disease (PD), and neurologically healthy control individuals, for instance, showed similar cell communication patterns in patients with IBD or PD (and no history of IBD) compared with healthy control individuals.

And in research using a single-cell genomics approach and a mouse model of lipopolysaccharide (LPS)-induced system neuroinflammation, microglia were found to preferentially communicate with peripheral myeloid cells rather than other microglia after peripheral LPS exposure.

“In saline-treated mice, the microglia are talking primarily to microglia, but in LPS-treated mice, microglia spend more time communicating with monocytes and T cells,” Merchak explained. “We see communication going from inside the brain to cells coming in from the periphery.”

In another experiment, 2 months of a high-fat, high-sugar diet in mice with an engineered predisposition to frontotemporal dementia led to significant upregulation of major histocompatibility complex class II (MHC II) expression on monocytes in the brain, she said, describing unpublished research. Because MHC II handles antigen presentation in the brain, the change signals increased central-peripheral immune crosstalk and increased brain inflammation.

 

State of Clinical Research

On the clinical side, Merchak said studies of gut microbiome-modulating therapies are currently not longitudinal enough to accurately study neurodegenerative diseases that may develop over decades. Still, her review of the literature — part of her 2024 article — suggests there is at least some preliminary clinical evidence for the use of probiotics/prebiotics/diet and fecal microbiota transplant (FMT) in several diseases.

• Parkinson’s Disease: “There has been some evidence,” Merchak said at the meeting, “for the treatment [with probiotics, prebiotics and diet] of nonmotor symptoms — things like gastrointestinal distress and mood changes — but no real evidence that such treatments can help with the motor symptoms we see in Parkinson’s.” Over 60 patients with PD have been treated with FMT, she said, with reduced GI distress and mixed results with motor symptoms.
• Alzheimer’s and related dementias: “Diet shows promise for cognitive outcomes, but there hasn’t been much evidence for probiotics,” she said. Her review found 17 patients diagnosed with dementia who were treated with FMT, “and for many of them, maintenance of cognitive function was reported — so no further decline — which is excellent.”
• Multiple Sclerosis: “We see higher quality-of-life measures in patients getting probiotics, prebiotics, and changes in diet,” Merchak said. “Again, most of this [relates to] mood and digestion, but some studies show a slowing of neurological damage as measured by MRI.” 

There are reports of 15 patients treated with FMT, and “three of these document full functional recovery,” she said, noting that longer follow-up is necessary as MS is characterized by relapsed and periods of recovery.

Merchak reported no financial disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Age-related neurodegenerative disorders — motor neuron diseases, demyelinating diseases, Alzheimer’s disease, and other proteinopathies — are at an “inflection point,” said researcher Andrea R. Merchak, PhD, with a fuller understanding of disease pathophysiology but an overall dearth of effective disease-modifying treatments.

And this, Merchak said at the Gut Microbiota for Health (GMFH) World Summit 2025, is where the gut microbiome comes in. “The gut-brain axis is important to take into consideration,” she urged, both for gut microbiome researchers — whose collaboration with neurologists and neuroscientists is essential — and for practicing gastroenterologists.

“We are the sum of our environmental exposures,” said Merchak, assistant research professor of neurology at the Indiana University School of Medicine, in Indianapolis. “So for your patient populations, remember you’re not only treating the diseases they’re coming to you with, you’re also treating them for a lifetime of healthy [brain] aging.”

At the center of a healthy aging brain are the brain-residing microglia and peripheral monocytes, she said. These immune cell populations are directly influenced by blood-brain barrier breakdown, inflammation, and gut permeability — and indirectly influenced by microbial products, gastrointestinal (GI) function, and bacterial diversity, Merchak said at the meeting, which was convened by AGA and the European Society of Neurogastroenterology and Motility.

“Many of us grew up learning that the brain is an immune-privileged site, but we’ve been establishing that this is fundamentally not true,” she said. “While the brain does have a privileged status, there are interactions with the blood, with the peripheral immune cells.”

Merchak coauthored a 2024 review in Neurotherapeutics in which she and her colleagues explained that the brain is “heavily connected with peripheral immune dynamics,” and that the gut — as the largest immune organ in the body — is a critical place for peripheral immune development, “thus influencing brain health.”

Gut microbiota interact with the brain via several mechanisms including microbiota-derived metabolites that enter circulation, direct communication via the vagus nerve, and modulation of the immune system, Merchak and her coauthors wrote. Leaky gut, they noted, can lead to an accumulation of inflammatory signals and cells that can exacerbate or induce the onset of neurodegenerative conditions.

As researchers better understand the role that GI dysfunction plays in neurodegenerative disease — as they identify microbiome signatures for predicting risk, for instance — there will be “opportunities to target the microbiome to prevent or reverse dysbiosis as a way to delay, arrest or prevent the onset and progression of neurodegenerative diseases,” they wrote.

At the GMFH meeting, Merchak described both ongoing preclinical research that is dissecting gut-brain communication, and preliminary clinical evidence for the use of gut microbiota-modulating therapies in neurodegenerative disease.

 

Support for a Gut-Focused Approach

Research on bile acid metabolism in multiple sclerosis (MS) and on peripheral inflammation in dementia exemplify the ongoing preclinical research uncovering the mechanisms of gut-brain communication, Merchak said.

The finding that bile acid metabolism modulates MS autoimmunity comes from research done by Merchak and a team at the University of Virginia, Charlottesville, Virginia, several years ago in which mice with experimental autoimmune encephalomyelitis (EAE) — an animal model of MS — were engineered for T cell specific knockout of the aryl hydrocarbon receptor (AHR). The AHR has been directly tied to MS, and T lymphocytes are known to play a central role in MS pathophysiology.

Blocking the activity of AHR in CD4-positive T cells significantly affected the production of bile acids and other metabolites in the microbiome — and the outcome of central nervous system autoimmunity. “Mice with high levels of bile acids, both primary and secondary, actually recovered from this EAE” and regained motor function, Merchak said at the GMFH meeting.

The potential impact of genetic manipulation on recovery was ruled out — and the role of bile acids confirmed — when, using the EAE model, gut bacteria from mice without AHR were transplanted into mice with AHR. The mice with AHR were able to recover, confirming that AHR can reprogram the gut microbiome and that “high levels of bile acid can lead to reduced autoimmunity in an MS model,” she said.

Other elements and stages of the research, which was published in PLOS Biology in 2023, showed increased apoptosis of CD4-positive immune cells in AHR-deficient mice and the ability of oral taurocholic acid — a bile acid that was especially high in mice without AHR — to reduce the severity of EAE, Merchak said.

Evidence for the role of gut and peripheral inflammation on neurodegeneration is building on numerous fronts, Merchak said. Unpublished research using spatial transcriptomics of colon biopsies from patients with inflammatory bowel disease (IBD), patients with Parkinson’s disease (PD), and neurologically healthy control individuals, for instance, showed similar cell communication patterns in patients with IBD or PD (and no history of IBD) compared with healthy control individuals.

And in research using a single-cell genomics approach and a mouse model of lipopolysaccharide (LPS)-induced system neuroinflammation, microglia were found to preferentially communicate with peripheral myeloid cells rather than other microglia after peripheral LPS exposure.

“In saline-treated mice, the microglia are talking primarily to microglia, but in LPS-treated mice, microglia spend more time communicating with monocytes and T cells,” Merchak explained. “We see communication going from inside the brain to cells coming in from the periphery.”

In another experiment, 2 months of a high-fat, high-sugar diet in mice with an engineered predisposition to frontotemporal dementia led to significant upregulation of major histocompatibility complex class II (MHC II) expression on monocytes in the brain, she said, describing unpublished research. Because MHC II handles antigen presentation in the brain, the change signals increased central-peripheral immune crosstalk and increased brain inflammation.

 

State of Clinical Research

On the clinical side, Merchak said studies of gut microbiome-modulating therapies are currently not longitudinal enough to accurately study neurodegenerative diseases that may develop over decades. Still, her review of the literature — part of her 2024 article — suggests there is at least some preliminary clinical evidence for the use of probiotics/prebiotics/diet and fecal microbiota transplant (FMT) in several diseases.

• Parkinson’s Disease: “There has been some evidence,” Merchak said at the meeting, “for the treatment [with probiotics, prebiotics and diet] of nonmotor symptoms — things like gastrointestinal distress and mood changes — but no real evidence that such treatments can help with the motor symptoms we see in Parkinson’s.” Over 60 patients with PD have been treated with FMT, she said, with reduced GI distress and mixed results with motor symptoms.
• Alzheimer’s and related dementias: “Diet shows promise for cognitive outcomes, but there hasn’t been much evidence for probiotics,” she said. Her review found 17 patients diagnosed with dementia who were treated with FMT, “and for many of them, maintenance of cognitive function was reported — so no further decline — which is excellent.”
• Multiple Sclerosis: “We see higher quality-of-life measures in patients getting probiotics, prebiotics, and changes in diet,” Merchak said. “Again, most of this [relates to] mood and digestion, but some studies show a slowing of neurological damage as measured by MRI.” 

There are reports of 15 patients treated with FMT, and “three of these document full functional recovery,” she said, noting that longer follow-up is necessary as MS is characterized by relapsed and periods of recovery.

Merchak reported no financial disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Age-related neurodegenerative disorders — motor neuron diseases, demyelinating diseases, Alzheimer’s disease, and other proteinopathies — are at an “inflection point,” said researcher Andrea R. Merchak, PhD, with a fuller understanding of disease pathophysiology but an overall dearth of effective disease-modifying treatments.

And this, Merchak said at the Gut Microbiota for Health (GMFH) World Summit 2025, is where the gut microbiome comes in. “The gut-brain axis is important to take into consideration,” she urged, both for gut microbiome researchers — whose collaboration with neurologists and neuroscientists is essential — and for practicing gastroenterologists.

“We are the sum of our environmental exposures,” said Merchak, assistant research professor of neurology at the Indiana University School of Medicine, in Indianapolis. “So for your patient populations, remember you’re not only treating the diseases they’re coming to you with, you’re also treating them for a lifetime of healthy [brain] aging.”

At the center of a healthy aging brain are the brain-residing microglia and peripheral monocytes, she said. These immune cell populations are directly influenced by blood-brain barrier breakdown, inflammation, and gut permeability — and indirectly influenced by microbial products, gastrointestinal (GI) function, and bacterial diversity, Merchak said at the meeting, which was convened by AGA and the European Society of Neurogastroenterology and Motility.

“Many of us grew up learning that the brain is an immune-privileged site, but we’ve been establishing that this is fundamentally not true,” she said. “While the brain does have a privileged status, there are interactions with the blood, with the peripheral immune cells.”

Merchak coauthored a 2024 review in Neurotherapeutics in which she and her colleagues explained that the brain is “heavily connected with peripheral immune dynamics,” and that the gut — as the largest immune organ in the body — is a critical place for peripheral immune development, “thus influencing brain health.”

Gut microbiota interact with the brain via several mechanisms including microbiota-derived metabolites that enter circulation, direct communication via the vagus nerve, and modulation of the immune system, Merchak and her coauthors wrote. Leaky gut, they noted, can lead to an accumulation of inflammatory signals and cells that can exacerbate or induce the onset of neurodegenerative conditions.

As researchers better understand the role that GI dysfunction plays in neurodegenerative disease — as they identify microbiome signatures for predicting risk, for instance — there will be “opportunities to target the microbiome to prevent or reverse dysbiosis as a way to delay, arrest or prevent the onset and progression of neurodegenerative diseases,” they wrote.

At the GMFH meeting, Merchak described both ongoing preclinical research that is dissecting gut-brain communication, and preliminary clinical evidence for the use of gut microbiota-modulating therapies in neurodegenerative disease.

 

Support for a Gut-Focused Approach

Research on bile acid metabolism in multiple sclerosis (MS) and on peripheral inflammation in dementia exemplify the ongoing preclinical research uncovering the mechanisms of gut-brain communication, Merchak said.

The finding that bile acid metabolism modulates MS autoimmunity comes from research done by Merchak and a team at the University of Virginia, Charlottesville, Virginia, several years ago in which mice with experimental autoimmune encephalomyelitis (EAE) — an animal model of MS — were engineered for T cell specific knockout of the aryl hydrocarbon receptor (AHR). The AHR has been directly tied to MS, and T lymphocytes are known to play a central role in MS pathophysiology.

Blocking the activity of AHR in CD4-positive T cells significantly affected the production of bile acids and other metabolites in the microbiome — and the outcome of central nervous system autoimmunity. “Mice with high levels of bile acids, both primary and secondary, actually recovered from this EAE” and regained motor function, Merchak said at the GMFH meeting.

The potential impact of genetic manipulation on recovery was ruled out — and the role of bile acids confirmed — when, using the EAE model, gut bacteria from mice without AHR were transplanted into mice with AHR. The mice with AHR were able to recover, confirming that AHR can reprogram the gut microbiome and that “high levels of bile acid can lead to reduced autoimmunity in an MS model,” she said.

Other elements and stages of the research, which was published in PLOS Biology in 2023, showed increased apoptosis of CD4-positive immune cells in AHR-deficient mice and the ability of oral taurocholic acid — a bile acid that was especially high in mice without AHR — to reduce the severity of EAE, Merchak said.

Evidence for the role of gut and peripheral inflammation on neurodegeneration is building on numerous fronts, Merchak said. Unpublished research using spatial transcriptomics of colon biopsies from patients with inflammatory bowel disease (IBD), patients with Parkinson’s disease (PD), and neurologically healthy control individuals, for instance, showed similar cell communication patterns in patients with IBD or PD (and no history of IBD) compared with healthy control individuals.

And in research using a single-cell genomics approach and a mouse model of lipopolysaccharide (LPS)-induced system neuroinflammation, microglia were found to preferentially communicate with peripheral myeloid cells rather than other microglia after peripheral LPS exposure.

“In saline-treated mice, the microglia are talking primarily to microglia, but in LPS-treated mice, microglia spend more time communicating with monocytes and T cells,” Merchak explained. “We see communication going from inside the brain to cells coming in from the periphery.”

In another experiment, 2 months of a high-fat, high-sugar diet in mice with an engineered predisposition to frontotemporal dementia led to significant upregulation of major histocompatibility complex class II (MHC II) expression on monocytes in the brain, she said, describing unpublished research. Because MHC II handles antigen presentation in the brain, the change signals increased central-peripheral immune crosstalk and increased brain inflammation.

 

State of Clinical Research

On the clinical side, Merchak said studies of gut microbiome-modulating therapies are currently not longitudinal enough to accurately study neurodegenerative diseases that may develop over decades. Still, her review of the literature — part of her 2024 article — suggests there is at least some preliminary clinical evidence for the use of probiotics/prebiotics/diet and fecal microbiota transplant (FMT) in several diseases.

• Parkinson’s Disease: “There has been some evidence,” Merchak said at the meeting, “for the treatment [with probiotics, prebiotics and diet] of nonmotor symptoms — things like gastrointestinal distress and mood changes — but no real evidence that such treatments can help with the motor symptoms we see in Parkinson’s.” Over 60 patients with PD have been treated with FMT, she said, with reduced GI distress and mixed results with motor symptoms.
• Alzheimer’s and related dementias: “Diet shows promise for cognitive outcomes, but there hasn’t been much evidence for probiotics,” she said. Her review found 17 patients diagnosed with dementia who were treated with FMT, “and for many of them, maintenance of cognitive function was reported — so no further decline — which is excellent.”
• Multiple Sclerosis: “We see higher quality-of-life measures in patients getting probiotics, prebiotics, and changes in diet,” Merchak said. “Again, most of this [relates to] mood and digestion, but some studies show a slowing of neurological damage as measured by MRI.” 

There are reports of 15 patients treated with FMT, and “three of these document full functional recovery,” she said, noting that longer follow-up is necessary as MS is characterized by relapsed and periods of recovery.

Merchak reported no financial disclosures.

A version of this article appeared on Medscape.com.

The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024. 

Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release. 

“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release. 

“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.

The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics. 

The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission. 

Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints. 

Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said. 

The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.

The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter. 

Use of the lowest effective recommended dosage to maintain therapeutic response is recommended. 

Full prescribing information and medication guide are available online.

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

The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024. 

Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release. 

“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release. 

“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.

The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics. 

The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission. 

Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints. 

Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said. 

The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.

The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter. 

Use of the lowest effective recommended dosage to maintain therapeutic response is recommended. 

Full prescribing information and medication guide are available online.

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

The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024. 

Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release. 

“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release. 

“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.

The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics. 

The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission. 

Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints. 

Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said. 

The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.

The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter. 

Use of the lowest effective recommended dosage to maintain therapeutic response is recommended. 

Full prescribing information and medication guide are available online.

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

Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).

A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.

The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.

 

Sensitivity Detection

In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.

To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.

 

Predictive Signature

Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.

For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.

These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD. By identifying individuals sensitive to specific emulsifiers, clinicians can tailor diets to reduce inflammation and potentially prevent disease onset in those at risk.

To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).

A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.

The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.

 

Sensitivity Detection

In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.

To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.

 

Predictive Signature

Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.

For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.

These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD. By identifying individuals sensitive to specific emulsifiers, clinicians can tailor diets to reduce inflammation and potentially prevent disease onset in those at risk.

To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).

A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.

The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.

 

Sensitivity Detection

In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.

To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.

 

Predictive Signature

Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.

For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.

These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD. By identifying individuals sensitive to specific emulsifiers, clinicians can tailor diets to reduce inflammation and potentially prevent disease onset in those at risk.

To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Circulating blood proteins could enable early identification of Crohn’s disease (CD) years before clinical signs, according to investigators.

The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported. 

“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.

Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted. 

Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.

First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature. 

In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87. 

While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.

Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.

“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”

These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.

Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs. 

The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation. 

In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.

Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.

“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.

This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.

Circulating blood proteins could enable early identification of Crohn’s disease (CD) years before clinical signs, according to investigators.

The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported. 

“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.

Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted. 

Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.

First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature. 

In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87. 

While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.

Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.

“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”

These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.

Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs. 

The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation. 

In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.

Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.

“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.

This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.

Circulating blood proteins could enable early identification of Crohn’s disease (CD) years before clinical signs, according to investigators.

The 29-protein biosignature, which was validated across multiple independent cohorts, could potentially open doors to new preclinical interventions, lead author Olle Grännö, MD, of Örebro University in Sweden, and colleagues reported. 

“Predictive biomarkers of future clinical onset of active inflammatory bowel disease could detect the disease during ‘a window of opportunity’ when the immune dysregulation is potentially reversible,” the investigators wrote in Gastroenterology.

Preclinical biomarker screening has proven effective in other immune-mediated diseases, such as type 1 diabetes, where risk stratification using autoantibodies enabled early intervention that delayed disease onset, they noted. 

Previous studies suggested similar potential for inflammatory bowel disease (IBD) via predictive autoantibodies and serum proteins, although the accuracy of these markers was not validated in external cohorts. The present study aimed to fill this validation gap.

First, the investigators measured 178 plasma proteins in blood samples taken from 312 individuals before they were diagnosed with IBD. Using machine learning, Dr. Grännö and colleagues compared these findings with blood-matched controls who remained free of IBD through follow-up. This process revealed the 29-protein signature. 

In the same discovery cohort, the panel of 29 proteins differentiated preclinical CD cases from controls with an area under the curve (AUC) of 0.85. The signature was then validated in an independent preclinical cohort of CD patients, with an AUC of 0.87. 

While accuracy increased in proximity to clinical disease onset, the model was still highly predictive up to 16 years before CD diagnosis, at which time the AUC was 0.82. The panel showed perfect performance among newly diagnosed CD patients, with an AUC of 1.0, supporting clinical relevance.

Predictive power was statistically significant but less compelling among individuals with preclinical ulcerative colitis (UC). In this IBD subgroup, AUC for identification and validation cohorts was 0.77 and 0.67, respectively, while newly diagnosed patients had an AUC of 0.95.

“In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD,” Dr. Grännö and colleagues wrote. “Contrarily, all proteins associated with preclinical UC were upregulated, and only one protein marker correlated with the time to diagnosis.”

These findings suggest that disruptions in gut barrier integrity and macrophage function precede clinical CD onset, they explained, potentially serving as an early signal of inflammation-driven intestinal damage. In contrast, the preclinical UC signature primarily involved upregulated inflammatory markers.

Dr. Grännö and colleagues also examined the influence of genetic and environmental factors by comparing preclinical IBD signatures in unrelated and related twin pairs. 

The CD biosignature had an AUC of 0.89 when comparing individuals with preclinical CD to matched external (unrelated) healthy twins. Predictive ability dropped significantly (AUC = 0.58) when comparing CD cases to their own healthy twin siblings, suggesting that genetic and shared environmental factors have a “predominant influence” on protein dysregulation. 

In contrast, AUC among unrelated vs related twin controls was more similar for UC, at 0.76 and 0.64, respectively, indicating “a limited impact” of genetic and environmental factors on the protein signature.

Altogether, this study reinforces the concept of a long preclinical phase in CD, and highlights the potential for early detection and intervention, according to the investigators.

“The long preclinical period in CD endorses the adoption of early preventive strategies (e.g., diet alterations and medication) to potentially attenuate disease progression and improve the natural history of CD,” they concluded.

This study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Örebro University Hospital Research Foundation, and others. The investigators disclosed relationships with Pfizer, Janssen, AbbVie, and others.

BERLIN — Ulcerative colitis (UC) patients who fail on first-line therapy appear to have better outcomes with vedolizumab (Entyvio) than with infliximab, suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.

Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.

The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.

The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.

 

The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.

Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.

 

Head-to-Head Trial

Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.

No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.

They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.

Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.

Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.

The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.

Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).

Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).

There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.

Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.

The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.

 

Questions Remain

Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.

“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.

This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.

Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”

“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.

Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”

Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.

The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.

“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.

The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.

A version of this article appeared on Medscape.com.

BERLIN — Ulcerative colitis (UC) patients who fail on first-line therapy appear to have better outcomes with vedolizumab (Entyvio) than with infliximab, suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.

Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.

The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.

The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.

 

The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.

Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.

 

Head-to-Head Trial

Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.

No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.

They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.

Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.

Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.

The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.

Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).

Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).

There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.

Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.

The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.

 

Questions Remain

Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.

“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.

This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.

Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”

“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.

Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”

Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.

The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.

“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.

The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.

A version of this article appeared on Medscape.com.

BERLIN — Ulcerative colitis (UC) patients who fail on first-line therapy appear to have better outcomes with vedolizumab (Entyvio) than with infliximab, suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.

Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the gastroenterology gepartment, CHU Rennes – Pontchaillou Hospital, France.

The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.

The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.

 

The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, AGAF, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, said in an interview.

Bouguen noted that the trial was unblinded at week 14 and that patients were followed up to week 54, data for which will be presented in the near future.

 

Head-to-Head Trial

Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.

No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.

They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.

Participants were randomly assigned to intravenous 300 mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.

Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 70 and patients, respectively, were available for assessment at week 14. Approximately 40% of the participants were women, and the average age was almost 40 years.

The mean total Mayo score at baseline was comparable between the two groups (9.0 vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 60% had experienced a loss of response to therapy.

Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P = .033).

Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P = .0507), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P = .0273).

There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.

Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.

The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.

 

Questions Remain

Study coinvestigator Matthieu Allez, MD, PhD, head of the gastroenterology department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, said in an interview that he was surprised by the findings.

“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.

This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.

Ali said that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”

“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.

Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”

Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.

The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.

“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.

The study was funded by the French national research program, with additional funding from Takeda. Bouguen declared relationships with Abbvie, Janssen, Lilly, Takeda, Celltrion, Sandoz, Galapagos, Tillotts, and Amgen. No other disclosures were reported.

A version of this article appeared on Medscape.com.

BERLIN — Induction therapy with subcutaneous guselkumab demonstrated significant efficacy in patients with moderately to severely active ulcerative colitis (UC), according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.

Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.

“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.

Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”

Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.

 

The ASTRO Study

Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.

After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).

All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).

Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).

“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.

The researchers also divided the results by prespecified subgroups based on previous treatments.

Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).

“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.

Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).

Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).

Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).

“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”

In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.

The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.

 

The GRAVITI Study

In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.

The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.

In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.

The co-primary endpoints were clinical remission and endoscopic response at week 12.

Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.

At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.

Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.

Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.

In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.

Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.

“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.

As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.

Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.

It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”

Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.

A version of this article appeared on Medscape.com.

BERLIN — Induction therapy with subcutaneous guselkumab demonstrated significant efficacy in patients with moderately to severely active ulcerative colitis (UC), according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.

Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.

“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.

Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”

Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.

 

The ASTRO Study

Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.

After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).

All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).

Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).

“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.

The researchers also divided the results by prespecified subgroups based on previous treatments.

Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).

“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.

Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).

Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).

Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).

“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”

In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.

The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.

 

The GRAVITI Study

In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.

The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.

In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.

The co-primary endpoints were clinical remission and endoscopic response at week 12.

Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.

At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.

Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.

Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.

In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.

Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.

“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.

As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.

Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.

It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”

Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.

A version of this article appeared on Medscape.com.

BERLIN — Induction therapy with subcutaneous guselkumab demonstrated significant efficacy in patients with moderately to severely active ulcerative colitis (UC), according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.

Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.

“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.

Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”

Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.

 

The ASTRO Study

Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.

After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).

All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).

Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).

“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.

The researchers also divided the results by prespecified subgroups based on previous treatments.

Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).

“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.

Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).

Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).

Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).

“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”

In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.

The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.

 

The GRAVITI Study

In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.

The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.

In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.

The co-primary endpoints were clinical remission and endoscopic response at week 12.

Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.

At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.

Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.

Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.

In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.

Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.

“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.

As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.

Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.

It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”

Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.

A version of this article appeared on Medscape.com.

BERLIN — Psychosocial factors, such as anxiety and depression, are associated with an increased risk for both self-reported “clinical” and symptomatic, or “hard,” flare in inflammatory bowel disease (IBD), suggested a study of UK patients.

The research was presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

“Despite clinical remission, there is a significant burden of psychosocial comorbidity in IBD patients,” said study presenter Lauranne A.A.P. Derikx, PhD, a gastroenterology researcher at Erasmus University MC, Rotterdam, the Netherlands.

“Anxiety, sleep, and somatization were associated with an increased risk of clinical flare, and depression and lack of exercise were associated with an increased risk of hard flare,” she said. “Altogether, this supports a holistic approach in IBD patients.”

 

Stephen E. Lupe, PsyD, director of behavioral medicine for the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic, Ohio, who was not involved in the study, agreed.

“Whole-person care is so important” in IBD, and this study is part of a growing literature making the connection between symptom flare and factors such as anxiety, depression, stress, and even trauma, he said in an interview.

 

Searching for Predictive Links

The relapsing and remitting disease course in IBD is dynamic and hard to predict, Derikx said. Unfortunately, clinicians don’t know which patients with IBD will develop a flare or when it will occur.

There’s a high prevalence of psychosocial comorbidity among patients with IBD and a “bidirectional relationship between psychosocial vulnerabilities” and the disease course via the gut-brain axis, Derikx noted.

To determine which psychosocial factors may be associated with and predictive of IBD flare, researchers analyzed data from the PREdiCCt study, a large prospective study of patients with IBD from 47 centers across the United Kingdom that aims to determine the factors associated with developing a flare.

The median age of PREdiCCT study participants was 44 years, median duration of IBD was 10 years, and 35% were receiving advanced IBD therapy. The median fecal calprotectin level was 49 mcg/g, although 18% of patients had a level > 250 mcg/g, Derikx noted.

To be included in PREdiCCT, patients must have received the diagnosis of IBD more than 6 months previously, had not change their medication for more than 2 months, and answered “yes” to the question: Do you think your disease has been well controlled in the past 1 month? The question was chosen as a measure of clinical remission.

The team collected stool samples and gathered information via questionnaires about lifestyle, diet, and other factors.

 

Depression and Anxiety Increase Risk

Researchers included 1641 patients — 830 with Crohn’s and 811 with ulcerative colitis or IBD unclassified (IBDU) — with complete datasets in their analysis of associations between psychosocial factors and IBD flare.

Baseline questionnaires identified moderate anxiety in 18.8% of participants, severe anxiety in 16.1%, moderate depression in 9.8%, severe depression in 5.7%, sleep disturbances in 46.4%, moderate somatization in 22.8%, severe somatization in 7.9%, insufficient exercise in 22.2%, and consumption of more than 14 units of alcohol in 24%.

After 24 months of follow-up, 36% of patients had experienced a clinical flare, defined as answering “no” to the question: Do you think your disease has been well controlled in the past 1 month/since you last logged in to the [study] portal?

In addition, 13% of patients experienced a hard flare, defined as a clinical flare plus C-reactive protein levels > 5 mg/L and/or a calprotectin level > 250 mcg/g and a change in IBD therapy.

Survival analyses with Cox frailty models adjusted for baseline fecal calprotectin, sex, index of multiple deprivation, hospital site, and patient age revealed statistically significant associations between several psychosocial factors and increased risk for flare.

Moderate anxiety in Crohn’s disease increased clinical flare risk (adjusted hazard ratio [aHR], 1.64), as did severe anxiety in both Crohn’s disease (aHR, 1.86) and ulcerative colitis/IBDU (aHR, 1.46). Moderate depression and severe depression increased the flare risk in ulcerative colitis/IBDU (aHR, 1.72 and 1.67, respectively). Also increasing clinical flare risk was poor sleep quality in Crohn’s disease (aHR, 1.58), and severe somatization in Crohn’s disease (aHR, 3.86) and ulcerative colitis/IBDU (aHR, 1.96).

Fewer psychosocial factors were associated with increased risk for hard flare: moderate depression in ulcerative colitis/IBDU (aHR, 2.5), severe somatization in Crohn’s disease (aHR, 2.34), and lack of exercise in ulcerative colitis/IBDU (aHR, 1.55).

 

Physician-Patient Disconnect

There is “very little correlation” between self-reported and symptomatic flare in IBD, Lupe said. “This happens all the time, where the gastroenterologist will come out of the endoscopy suite and go: ‘You’re in remission.’ And the patient goes: ‘What are you talking about? I’m still going to the bathroom 20 times a day.’ ”

Now there are data showing that, if the care team undertakes behavioral work with patients who have IBD, “the medications work more effectively,” Lupe said.

“I think medicine is in a point of transition right now,” he added. “We’re (moving from) looking at people as disease states and ‘how do I treat the disease’ to ‘how do I take care of this human being,’ knowing that everything this human being does, including everything we put in our mouth, everything we experience, changes what happens inside our body, and it’s measurable.”

The PREdiCCt study is sponsored by the University of Edinburgh, Scotland. Derikx declared relationships with AbbVie, Janssen Pharmaceuticals, Sandoz, Galapagos, and Pfizer. Other authors also declared relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

BERLIN — Psychosocial factors, such as anxiety and depression, are associated with an increased risk for both self-reported “clinical” and symptomatic, or “hard,” flare in inflammatory bowel disease (IBD), suggested a study of UK patients.

The research was presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

“Despite clinical remission, there is a significant burden of psychosocial comorbidity in IBD patients,” said study presenter Lauranne A.A.P. Derikx, PhD, a gastroenterology researcher at Erasmus University MC, Rotterdam, the Netherlands.

“Anxiety, sleep, and somatization were associated with an increased risk of clinical flare, and depression and lack of exercise were associated with an increased risk of hard flare,” she said. “Altogether, this supports a holistic approach in IBD patients.”

 

Stephen E. Lupe, PsyD, director of behavioral medicine for the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic, Ohio, who was not involved in the study, agreed.

“Whole-person care is so important” in IBD, and this study is part of a growing literature making the connection between symptom flare and factors such as anxiety, depression, stress, and even trauma, he said in an interview.

 

Searching for Predictive Links

The relapsing and remitting disease course in IBD is dynamic and hard to predict, Derikx said. Unfortunately, clinicians don’t know which patients with IBD will develop a flare or when it will occur.

There’s a high prevalence of psychosocial comorbidity among patients with IBD and a “bidirectional relationship between psychosocial vulnerabilities” and the disease course via the gut-brain axis, Derikx noted.

To determine which psychosocial factors may be associated with and predictive of IBD flare, researchers analyzed data from the PREdiCCt study, a large prospective study of patients with IBD from 47 centers across the United Kingdom that aims to determine the factors associated with developing a flare.

The median age of PREdiCCT study participants was 44 years, median duration of IBD was 10 years, and 35% were receiving advanced IBD therapy. The median fecal calprotectin level was 49 mcg/g, although 18% of patients had a level > 250 mcg/g, Derikx noted.

To be included in PREdiCCT, patients must have received the diagnosis of IBD more than 6 months previously, had not change their medication for more than 2 months, and answered “yes” to the question: Do you think your disease has been well controlled in the past 1 month? The question was chosen as a measure of clinical remission.

The team collected stool samples and gathered information via questionnaires about lifestyle, diet, and other factors.

 

Depression and Anxiety Increase Risk

Researchers included 1641 patients — 830 with Crohn’s and 811 with ulcerative colitis or IBD unclassified (IBDU) — with complete datasets in their analysis of associations between psychosocial factors and IBD flare.

Baseline questionnaires identified moderate anxiety in 18.8% of participants, severe anxiety in 16.1%, moderate depression in 9.8%, severe depression in 5.7%, sleep disturbances in 46.4%, moderate somatization in 22.8%, severe somatization in 7.9%, insufficient exercise in 22.2%, and consumption of more than 14 units of alcohol in 24%.

After 24 months of follow-up, 36% of patients had experienced a clinical flare, defined as answering “no” to the question: Do you think your disease has been well controlled in the past 1 month/since you last logged in to the [study] portal?

In addition, 13% of patients experienced a hard flare, defined as a clinical flare plus C-reactive protein levels > 5 mg/L and/or a calprotectin level > 250 mcg/g and a change in IBD therapy.

Survival analyses with Cox frailty models adjusted for baseline fecal calprotectin, sex, index of multiple deprivation, hospital site, and patient age revealed statistically significant associations between several psychosocial factors and increased risk for flare.

Moderate anxiety in Crohn’s disease increased clinical flare risk (adjusted hazard ratio [aHR], 1.64), as did severe anxiety in both Crohn’s disease (aHR, 1.86) and ulcerative colitis/IBDU (aHR, 1.46). Moderate depression and severe depression increased the flare risk in ulcerative colitis/IBDU (aHR, 1.72 and 1.67, respectively). Also increasing clinical flare risk was poor sleep quality in Crohn’s disease (aHR, 1.58), and severe somatization in Crohn’s disease (aHR, 3.86) and ulcerative colitis/IBDU (aHR, 1.96).

Fewer psychosocial factors were associated with increased risk for hard flare: moderate depression in ulcerative colitis/IBDU (aHR, 2.5), severe somatization in Crohn’s disease (aHR, 2.34), and lack of exercise in ulcerative colitis/IBDU (aHR, 1.55).

 

Physician-Patient Disconnect

There is “very little correlation” between self-reported and symptomatic flare in IBD, Lupe said. “This happens all the time, where the gastroenterologist will come out of the endoscopy suite and go: ‘You’re in remission.’ And the patient goes: ‘What are you talking about? I’m still going to the bathroom 20 times a day.’ ”

Now there are data showing that, if the care team undertakes behavioral work with patients who have IBD, “the medications work more effectively,” Lupe said.

“I think medicine is in a point of transition right now,” he added. “We’re (moving from) looking at people as disease states and ‘how do I treat the disease’ to ‘how do I take care of this human being,’ knowing that everything this human being does, including everything we put in our mouth, everything we experience, changes what happens inside our body, and it’s measurable.”

The PREdiCCt study is sponsored by the University of Edinburgh, Scotland. Derikx declared relationships with AbbVie, Janssen Pharmaceuticals, Sandoz, Galapagos, and Pfizer. Other authors also declared relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

BERLIN — Psychosocial factors, such as anxiety and depression, are associated with an increased risk for both self-reported “clinical” and symptomatic, or “hard,” flare in inflammatory bowel disease (IBD), suggested a study of UK patients.

The research was presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

“Despite clinical remission, there is a significant burden of psychosocial comorbidity in IBD patients,” said study presenter Lauranne A.A.P. Derikx, PhD, a gastroenterology researcher at Erasmus University MC, Rotterdam, the Netherlands.

“Anxiety, sleep, and somatization were associated with an increased risk of clinical flare, and depression and lack of exercise were associated with an increased risk of hard flare,” she said. “Altogether, this supports a holistic approach in IBD patients.”

 

Stephen E. Lupe, PsyD, director of behavioral medicine for the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic, Ohio, who was not involved in the study, agreed.

“Whole-person care is so important” in IBD, and this study is part of a growing literature making the connection between symptom flare and factors such as anxiety, depression, stress, and even trauma, he said in an interview.

 

Searching for Predictive Links

The relapsing and remitting disease course in IBD is dynamic and hard to predict, Derikx said. Unfortunately, clinicians don’t know which patients with IBD will develop a flare or when it will occur.

There’s a high prevalence of psychosocial comorbidity among patients with IBD and a “bidirectional relationship between psychosocial vulnerabilities” and the disease course via the gut-brain axis, Derikx noted.

To determine which psychosocial factors may be associated with and predictive of IBD flare, researchers analyzed data from the PREdiCCt study, a large prospective study of patients with IBD from 47 centers across the United Kingdom that aims to determine the factors associated with developing a flare.

The median age of PREdiCCT study participants was 44 years, median duration of IBD was 10 years, and 35% were receiving advanced IBD therapy. The median fecal calprotectin level was 49 mcg/g, although 18% of patients had a level > 250 mcg/g, Derikx noted.

To be included in PREdiCCT, patients must have received the diagnosis of IBD more than 6 months previously, had not change their medication for more than 2 months, and answered “yes” to the question: Do you think your disease has been well controlled in the past 1 month? The question was chosen as a measure of clinical remission.

The team collected stool samples and gathered information via questionnaires about lifestyle, diet, and other factors.

 

Depression and Anxiety Increase Risk

Researchers included 1641 patients — 830 with Crohn’s and 811 with ulcerative colitis or IBD unclassified (IBDU) — with complete datasets in their analysis of associations between psychosocial factors and IBD flare.

Baseline questionnaires identified moderate anxiety in 18.8% of participants, severe anxiety in 16.1%, moderate depression in 9.8%, severe depression in 5.7%, sleep disturbances in 46.4%, moderate somatization in 22.8%, severe somatization in 7.9%, insufficient exercise in 22.2%, and consumption of more than 14 units of alcohol in 24%.

After 24 months of follow-up, 36% of patients had experienced a clinical flare, defined as answering “no” to the question: Do you think your disease has been well controlled in the past 1 month/since you last logged in to the [study] portal?

In addition, 13% of patients experienced a hard flare, defined as a clinical flare plus C-reactive protein levels > 5 mg/L and/or a calprotectin level > 250 mcg/g and a change in IBD therapy.

Survival analyses with Cox frailty models adjusted for baseline fecal calprotectin, sex, index of multiple deprivation, hospital site, and patient age revealed statistically significant associations between several psychosocial factors and increased risk for flare.

Moderate anxiety in Crohn’s disease increased clinical flare risk (adjusted hazard ratio [aHR], 1.64), as did severe anxiety in both Crohn’s disease (aHR, 1.86) and ulcerative colitis/IBDU (aHR, 1.46). Moderate depression and severe depression increased the flare risk in ulcerative colitis/IBDU (aHR, 1.72 and 1.67, respectively). Also increasing clinical flare risk was poor sleep quality in Crohn’s disease (aHR, 1.58), and severe somatization in Crohn’s disease (aHR, 3.86) and ulcerative colitis/IBDU (aHR, 1.96).

Fewer psychosocial factors were associated with increased risk for hard flare: moderate depression in ulcerative colitis/IBDU (aHR, 2.5), severe somatization in Crohn’s disease (aHR, 2.34), and lack of exercise in ulcerative colitis/IBDU (aHR, 1.55).

 

Physician-Patient Disconnect

There is “very little correlation” between self-reported and symptomatic flare in IBD, Lupe said. “This happens all the time, where the gastroenterologist will come out of the endoscopy suite and go: ‘You’re in remission.’ And the patient goes: ‘What are you talking about? I’m still going to the bathroom 20 times a day.’ ”

Now there are data showing that, if the care team undertakes behavioral work with patients who have IBD, “the medications work more effectively,” Lupe said.

“I think medicine is in a point of transition right now,” he added. “We’re (moving from) looking at people as disease states and ‘how do I treat the disease’ to ‘how do I take care of this human being,’ knowing that everything this human being does, including everything we put in our mouth, everything we experience, changes what happens inside our body, and it’s measurable.”

The PREdiCCt study is sponsored by the University of Edinburgh, Scotland. Derikx declared relationships with AbbVie, Janssen Pharmaceuticals, Sandoz, Galapagos, and Pfizer. Other authors also declared relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

BERLIN — Gut microbial biomarkers identified using machine learning can differentiate patients with inflammatory bowel disease (IBD) from healthy control individuals, according to a study presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

Of the four techniques the researchers tested, a “machine-learning approach achieves the highest diagnostic accuracy, effectively distinguishing IBD and particularly differentiating Crohn’s disease from healthy controls in independent cohorts,” said study presenter Jee-Won Choi, department of biology, Kyung Hee University, Seoul, Republic of Korea.

“Integrating microbial markers with conventional diagnostics could enhance [their] clinical utility,” Choi said. However, further research is needed to determine the long-term validity of the biomarkers.

Some experts questioned the reliability of the markers for IBD diagnosis because of the makeup of study populations, which included patients with known IBD who likely have undergone treatment that may have altered their gut microbiomes.

 

Biomarkers Found and Tested

The gut microbiota exists in two states: Eubiosis, which supports health, and inflammatory dysbiosis, an imbalanced state associated with disease, most notably IBD, Choi noted.

Although many studies have explored the differences between these two states, there have been three major challenges in identifying IBD biomarkers: The studies have had small sample sizes, they’ve concentrated on a single analytical approach, and they’ve had low reproducibility.

To overcome those challenges, researchers used a large-scale dataset and used multiple methods to determine which analytical approach yielded the most reliable results, Choi said. They validated their results in three independent cohorts with diverse populations.

The study included 414 patients with Crohn’s disease, 880 with ulcerative colitis, and 2467 healthy control individuals from 21 centers in the Republic of Korea. Their gut microbiota profiles were analyzed from stool samples using 16S ribosomal RNA gene sequencing.

Researchers used four techniques to identify potential IBD biomarkers in the samples: differential abundance analysis, supervised random forest machine learning, unsupervised network analysis, and literature-based curation.

Biomarker candidates generated by these methods were then compared for their diagnostic ability using a machine learning model. The findings were tested in three independent cohorts — one domestic and one international population, both of which included patients with IBD and healthy control individuals, and one dataset of patients without IBD.

The results showed that there were distinct differences in the microbial composition between healthy control individuals and patients with Crohn’s disease and with ulcerative colitis. Patients with IBD, particularly those with Crohn’s disease, consistently had a significantly higher prevalence of dysbiosis, Choi said.

Each of the four analytical techniques revealed distinct microbial biomarkers associated with IBD in general, as well as with Crohn’s disease and ulcerative colitis individually.

When comparing IBD patients overall with healthy control individuals, supervised machine learning resulted in the most effective biomarker sets for distinguishing between groups, with the area under the receiver operating characteristics curve (AUC) reaching 0.971. By comparison, the AUC results were 0.94 for literature-based curation, 0.924 for differential abundance analyses, and 0.914 for unsupervised network analysis.

Supervised machine learning also outperformed the other techniques when distinguishing between healthy control individuals and patients with ulcerative colitis (AUC, 0.958), and between patients with ulcerative colitis and those with Crohn’s disease (AUC, 0.902).

All the techniques performed strongly when distinguishing between healthy control individuals and patients with Crohn’s disease, with AUCs ranging from 0.911 to 0.95.

When the researchers turned to the independent datasets, they found that the biomarkers were able to distinguish between healthy control individuals and patients with IBD in general and particularly between healthy control individuals and those with Crohn’s disease, with AUCs of 0.969 in the domestic cohort and 0.848 in the international cohort.

The non-IBD cohort also demonstrated that the biomarkers were able to differentiate patients with metabolic dysfunction–associated steatotic liver disease, colorectal cancer, rheumatoid arthritis, and irritable bowel syndrome from those with ulcerative colitis and Crohn’s disease with a high degree of accuracy (AUCs ranging from 0.97 to 0.999).

 

Diagnostic Utility Questioned

Speaking from the audience, James Lindsay, PhD, professor of inflammatory bowel disease, Barts and The London School of Medicine and Dentistry, England, questioned the utility of the findings.

“Obviously, all these patients had IBD, and so they will have had treatment with antibiotics, etc,” he said. “Surely the right validation cohort would be a group of people who have not yet been diagnosed with IBD to see whether your biomarker is able to separate those because the reason that people with IBD will have a difference is all the reasons that you have explained, ie, these patients were on treatment at the time that you took the samples.”

As a result, the biomarker panel isn’t for diagnosis but to confirm known disease, he added.

It’s important to look for microbiome signals of IBD, session co-chair, Lissy de Ridder, MD, PhD, associate professor of pediatric gastroenterology, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands, said in an interview.

De Ridder agreed that the biomarkers need to be validated in patients who aren’t on treatments that could affect their gut microbiomes. Not only do medications for IBD make a big difference but also do other drugs such as proton-pump inhibitors and antibiotics, as well as dietary interventions.

“Having said that, because it’s a large population, that’s always a good start to take lessons from and then go more into the details” in further analyses, de Ridder added.

This research was funded by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

BERLIN — Gut microbial biomarkers identified using machine learning can differentiate patients with inflammatory bowel disease (IBD) from healthy control individuals, according to a study presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

Of the four techniques the researchers tested, a “machine-learning approach achieves the highest diagnostic accuracy, effectively distinguishing IBD and particularly differentiating Crohn’s disease from healthy controls in independent cohorts,” said study presenter Jee-Won Choi, department of biology, Kyung Hee University, Seoul, Republic of Korea.

“Integrating microbial markers with conventional diagnostics could enhance [their] clinical utility,” Choi said. However, further research is needed to determine the long-term validity of the biomarkers.

Some experts questioned the reliability of the markers for IBD diagnosis because of the makeup of study populations, which included patients with known IBD who likely have undergone treatment that may have altered their gut microbiomes.

 

Biomarkers Found and Tested

The gut microbiota exists in two states: Eubiosis, which supports health, and inflammatory dysbiosis, an imbalanced state associated with disease, most notably IBD, Choi noted.

Although many studies have explored the differences between these two states, there have been three major challenges in identifying IBD biomarkers: The studies have had small sample sizes, they’ve concentrated on a single analytical approach, and they’ve had low reproducibility.

To overcome those challenges, researchers used a large-scale dataset and used multiple methods to determine which analytical approach yielded the most reliable results, Choi said. They validated their results in three independent cohorts with diverse populations.

The study included 414 patients with Crohn’s disease, 880 with ulcerative colitis, and 2467 healthy control individuals from 21 centers in the Republic of Korea. Their gut microbiota profiles were analyzed from stool samples using 16S ribosomal RNA gene sequencing.

Researchers used four techniques to identify potential IBD biomarkers in the samples: differential abundance analysis, supervised random forest machine learning, unsupervised network analysis, and literature-based curation.

Biomarker candidates generated by these methods were then compared for their diagnostic ability using a machine learning model. The findings were tested in three independent cohorts — one domestic and one international population, both of which included patients with IBD and healthy control individuals, and one dataset of patients without IBD.

The results showed that there were distinct differences in the microbial composition between healthy control individuals and patients with Crohn’s disease and with ulcerative colitis. Patients with IBD, particularly those with Crohn’s disease, consistently had a significantly higher prevalence of dysbiosis, Choi said.

Each of the four analytical techniques revealed distinct microbial biomarkers associated with IBD in general, as well as with Crohn’s disease and ulcerative colitis individually.

When comparing IBD patients overall with healthy control individuals, supervised machine learning resulted in the most effective biomarker sets for distinguishing between groups, with the area under the receiver operating characteristics curve (AUC) reaching 0.971. By comparison, the AUC results were 0.94 for literature-based curation, 0.924 for differential abundance analyses, and 0.914 for unsupervised network analysis.

Supervised machine learning also outperformed the other techniques when distinguishing between healthy control individuals and patients with ulcerative colitis (AUC, 0.958), and between patients with ulcerative colitis and those with Crohn’s disease (AUC, 0.902).

All the techniques performed strongly when distinguishing between healthy control individuals and patients with Crohn’s disease, with AUCs ranging from 0.911 to 0.95.

When the researchers turned to the independent datasets, they found that the biomarkers were able to distinguish between healthy control individuals and patients with IBD in general and particularly between healthy control individuals and those with Crohn’s disease, with AUCs of 0.969 in the domestic cohort and 0.848 in the international cohort.

The non-IBD cohort also demonstrated that the biomarkers were able to differentiate patients with metabolic dysfunction–associated steatotic liver disease, colorectal cancer, rheumatoid arthritis, and irritable bowel syndrome from those with ulcerative colitis and Crohn’s disease with a high degree of accuracy (AUCs ranging from 0.97 to 0.999).

 

Diagnostic Utility Questioned

Speaking from the audience, James Lindsay, PhD, professor of inflammatory bowel disease, Barts and The London School of Medicine and Dentistry, England, questioned the utility of the findings.

“Obviously, all these patients had IBD, and so they will have had treatment with antibiotics, etc,” he said. “Surely the right validation cohort would be a group of people who have not yet been diagnosed with IBD to see whether your biomarker is able to separate those because the reason that people with IBD will have a difference is all the reasons that you have explained, ie, these patients were on treatment at the time that you took the samples.”

As a result, the biomarker panel isn’t for diagnosis but to confirm known disease, he added.

It’s important to look for microbiome signals of IBD, session co-chair, Lissy de Ridder, MD, PhD, associate professor of pediatric gastroenterology, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands, said in an interview.

De Ridder agreed that the biomarkers need to be validated in patients who aren’t on treatments that could affect their gut microbiomes. Not only do medications for IBD make a big difference but also do other drugs such as proton-pump inhibitors and antibiotics, as well as dietary interventions.

“Having said that, because it’s a large population, that’s always a good start to take lessons from and then go more into the details” in further analyses, de Ridder added.

This research was funded by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

BERLIN — Gut microbial biomarkers identified using machine learning can differentiate patients with inflammatory bowel disease (IBD) from healthy control individuals, according to a study presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

Of the four techniques the researchers tested, a “machine-learning approach achieves the highest diagnostic accuracy, effectively distinguishing IBD and particularly differentiating Crohn’s disease from healthy controls in independent cohorts,” said study presenter Jee-Won Choi, department of biology, Kyung Hee University, Seoul, Republic of Korea.

“Integrating microbial markers with conventional diagnostics could enhance [their] clinical utility,” Choi said. However, further research is needed to determine the long-term validity of the biomarkers.

Some experts questioned the reliability of the markers for IBD diagnosis because of the makeup of study populations, which included patients with known IBD who likely have undergone treatment that may have altered their gut microbiomes.

 

Biomarkers Found and Tested

The gut microbiota exists in two states: Eubiosis, which supports health, and inflammatory dysbiosis, an imbalanced state associated with disease, most notably IBD, Choi noted.

Although many studies have explored the differences between these two states, there have been three major challenges in identifying IBD biomarkers: The studies have had small sample sizes, they’ve concentrated on a single analytical approach, and they’ve had low reproducibility.

To overcome those challenges, researchers used a large-scale dataset and used multiple methods to determine which analytical approach yielded the most reliable results, Choi said. They validated their results in three independent cohorts with diverse populations.

The study included 414 patients with Crohn’s disease, 880 with ulcerative colitis, and 2467 healthy control individuals from 21 centers in the Republic of Korea. Their gut microbiota profiles were analyzed from stool samples using 16S ribosomal RNA gene sequencing.

Researchers used four techniques to identify potential IBD biomarkers in the samples: differential abundance analysis, supervised random forest machine learning, unsupervised network analysis, and literature-based curation.

Biomarker candidates generated by these methods were then compared for their diagnostic ability using a machine learning model. The findings were tested in three independent cohorts — one domestic and one international population, both of which included patients with IBD and healthy control individuals, and one dataset of patients without IBD.

The results showed that there were distinct differences in the microbial composition between healthy control individuals and patients with Crohn’s disease and with ulcerative colitis. Patients with IBD, particularly those with Crohn’s disease, consistently had a significantly higher prevalence of dysbiosis, Choi said.

Each of the four analytical techniques revealed distinct microbial biomarkers associated with IBD in general, as well as with Crohn’s disease and ulcerative colitis individually.

When comparing IBD patients overall with healthy control individuals, supervised machine learning resulted in the most effective biomarker sets for distinguishing between groups, with the area under the receiver operating characteristics curve (AUC) reaching 0.971. By comparison, the AUC results were 0.94 for literature-based curation, 0.924 for differential abundance analyses, and 0.914 for unsupervised network analysis.

Supervised machine learning also outperformed the other techniques when distinguishing between healthy control individuals and patients with ulcerative colitis (AUC, 0.958), and between patients with ulcerative colitis and those with Crohn’s disease (AUC, 0.902).

All the techniques performed strongly when distinguishing between healthy control individuals and patients with Crohn’s disease, with AUCs ranging from 0.911 to 0.95.

When the researchers turned to the independent datasets, they found that the biomarkers were able to distinguish between healthy control individuals and patients with IBD in general and particularly between healthy control individuals and those with Crohn’s disease, with AUCs of 0.969 in the domestic cohort and 0.848 in the international cohort.

The non-IBD cohort also demonstrated that the biomarkers were able to differentiate patients with metabolic dysfunction–associated steatotic liver disease, colorectal cancer, rheumatoid arthritis, and irritable bowel syndrome from those with ulcerative colitis and Crohn’s disease with a high degree of accuracy (AUCs ranging from 0.97 to 0.999).

 

Diagnostic Utility Questioned

Speaking from the audience, James Lindsay, PhD, professor of inflammatory bowel disease, Barts and The London School of Medicine and Dentistry, England, questioned the utility of the findings.

“Obviously, all these patients had IBD, and so they will have had treatment with antibiotics, etc,” he said. “Surely the right validation cohort would be a group of people who have not yet been diagnosed with IBD to see whether your biomarker is able to separate those because the reason that people with IBD will have a difference is all the reasons that you have explained, ie, these patients were on treatment at the time that you took the samples.”

As a result, the biomarker panel isn’t for diagnosis but to confirm known disease, he added.

It’s important to look for microbiome signals of IBD, session co-chair, Lissy de Ridder, MD, PhD, associate professor of pediatric gastroenterology, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands, said in an interview.

De Ridder agreed that the biomarkers need to be validated in patients who aren’t on treatments that could affect their gut microbiomes. Not only do medications for IBD make a big difference but also do other drugs such as proton-pump inhibitors and antibiotics, as well as dietary interventions.

“Having said that, because it’s a large population, that’s always a good start to take lessons from and then go more into the details” in further analyses, de Ridder added.

This research was funded by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

BERLIN — Lusvertikimab, a first-in-class interleukin (IL)–7 receptor antagonist, demonstrated clinical and endoscopic efficacy in patients with moderate to severe ulcerative colitis (UC) in the 10-week induction period of a randomized, placebo-controlled, phase 2 clinical trial.

Lusvertikimab is unique in targeting the IL-7 receptor, a key player in immune-mediated inflammation.

“We have a new mode of action in ulcerative colitis,” with a strong safety profile, lead investigator, Arnaud Bourreille, MD, associate professor of gastroenterology from Nantes University Hospital, France, said in an interview.

“We achieved the primary endpoint” — improvement in the modified Mayo score (MMS) from baseline to week 10 — “for both the low dose and the high dose of lusvertikimab,” said Bourreille, who presented the findings at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress. “For us practitioners, this is very good news.”

Current treatment options for UC remain limited, especially for patients with an inadequate response to biologics or small molecules.

Overall, biologics are only effective in around half the patients, Bourreille noted. We need other treatments that have different mechanisms of action, as is the case with lusvertikimab.

The multicenter, double-blind CoTikiS study evaluated the IL-7 receptor antagonist in 136 adults with moderately to severely active UC (MMS, 4-9) and inadequate response to conventional therapies and/or failure to advanced therapies. Around 40% of the patients were exposed to one or more biologics.

The 50-week study had a 10-week induction period with two doses of lusvertikimab (450 and 850 mg), followed by a 24-week open-label extension, where patients received infusions of the high dose (850 mg) every 4 weeks, and a 16-week safety follow-up period free of treatment.

For the induction period, patients were randomized 1:1:1 to receive placebo (n = 49), 450 mg lusvertikimab (n = 35), or 850 mg lusvertikimab (n = 50) intravenously at weeks 0, 2, and 6. The diagnosis in two patients was modified to Crohn’s disease; therefore, they were not included.

In meeting the trial’s primary endpoint, lusvertikimab significantly reduced disease severity, compared with placebo, at week 10 in both dose groups separately and when pooled.

The MMS in the 450-mg group showed a difference of –1.16 points vs placebo (P = .019), whereas in the 850-mg group, the MMS showed a difference of –0.9 points vs placebo (P = .036). In the pooled group, the difference was –1.00 points vs placebo (P = .010).

The secondary endpoints of clinical remission and endoscopic remission also favored lusvertikimab for the pooled doses vs placebo, at 16% vs 4% (odds ratio [OR], 4.25; P = .066) and 25% vs 13% (OR, 2.33; P = .120), respectively.

For the other secondary endpoints, 32% achieved endoscopic improvement in the pooled group vs 13% in the placebo group (OR, 3.29; P = .027), and the mean score change in the UC Endoscopic Index of Severity was –1.35 for the pooled group vs –0.32 for the placebo group (P = .007).

Fecal calprotectin was reduced by 830 μg/g in the 450-mg group (P =.009), by 635 μg/g in the 850-mg group (P = .018), and 716 μg/g in the pooled group. It was increased by 189 μg/g in the placebo group (P = .004).

No safety concerns were reported.

Bourreille noted that there was a little more lymphopenia in patients on lusvertikimab vs placebo, which is explained by the drug’s mechanism of action. However, “it was transient lymphopenia, without any infection and without any need to interrupt the treatment.”

Next, Bourreille said, we need to demonstrate the efficacy and the safety of the drug in the long term.

“There may be a place for lusvertikimab in patients with Crohn’s disease because the mechanism of action of IL-7 receptor antagonist would potentially have good efficacy in that disease too,” he added.

Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Greece, who comoderated the session, pointed out that the results supported further clinical development of lusvertikimab.

“As elevated mucosal IL-7/IL-7 [receptor] expression predicts refractoriness to currently used biologic therapies, it would be very interesting to see the potential of lusvertikimab as a treatment for patients who were exposed to advanced therapy or as part of combination therapeutics,” he said.

The study was funded by OSE Immunotherapeutics. Bourreille received funding from OSE Immunotherapeutics; grants from Takeda and Mauna Kea Technologies; and personal fees from AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. Bamias reported receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as adviser/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, Johnson & Johnson, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.

A version of this article appeared on Medscape.com.

BERLIN — Lusvertikimab, a first-in-class interleukin (IL)–7 receptor antagonist, demonstrated clinical and endoscopic efficacy in patients with moderate to severe ulcerative colitis (UC) in the 10-week induction period of a randomized, placebo-controlled, phase 2 clinical trial.

Lusvertikimab is unique in targeting the IL-7 receptor, a key player in immune-mediated inflammation.

“We have a new mode of action in ulcerative colitis,” with a strong safety profile, lead investigator, Arnaud Bourreille, MD, associate professor of gastroenterology from Nantes University Hospital, France, said in an interview.

“We achieved the primary endpoint” — improvement in the modified Mayo score (MMS) from baseline to week 10 — “for both the low dose and the high dose of lusvertikimab,” said Bourreille, who presented the findings at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress. “For us practitioners, this is very good news.”

Current treatment options for UC remain limited, especially for patients with an inadequate response to biologics or small molecules.

Overall, biologics are only effective in around half the patients, Bourreille noted. We need other treatments that have different mechanisms of action, as is the case with lusvertikimab.

The multicenter, double-blind CoTikiS study evaluated the IL-7 receptor antagonist in 136 adults with moderately to severely active UC (MMS, 4-9) and inadequate response to conventional therapies and/or failure to advanced therapies. Around 40% of the patients were exposed to one or more biologics.

The 50-week study had a 10-week induction period with two doses of lusvertikimab (450 and 850 mg), followed by a 24-week open-label extension, where patients received infusions of the high dose (850 mg) every 4 weeks, and a 16-week safety follow-up period free of treatment.

For the induction period, patients were randomized 1:1:1 to receive placebo (n = 49), 450 mg lusvertikimab (n = 35), or 850 mg lusvertikimab (n = 50) intravenously at weeks 0, 2, and 6. The diagnosis in two patients was modified to Crohn’s disease; therefore, they were not included.

In meeting the trial’s primary endpoint, lusvertikimab significantly reduced disease severity, compared with placebo, at week 10 in both dose groups separately and when pooled.

The MMS in the 450-mg group showed a difference of –1.16 points vs placebo (P = .019), whereas in the 850-mg group, the MMS showed a difference of –0.9 points vs placebo (P = .036). In the pooled group, the difference was –1.00 points vs placebo (P = .010).

The secondary endpoints of clinical remission and endoscopic remission also favored lusvertikimab for the pooled doses vs placebo, at 16% vs 4% (odds ratio [OR], 4.25; P = .066) and 25% vs 13% (OR, 2.33; P = .120), respectively.

For the other secondary endpoints, 32% achieved endoscopic improvement in the pooled group vs 13% in the placebo group (OR, 3.29; P = .027), and the mean score change in the UC Endoscopic Index of Severity was –1.35 for the pooled group vs –0.32 for the placebo group (P = .007).

Fecal calprotectin was reduced by 830 μg/g in the 450-mg group (P =.009), by 635 μg/g in the 850-mg group (P = .018), and 716 μg/g in the pooled group. It was increased by 189 μg/g in the placebo group (P = .004).

No safety concerns were reported.

Bourreille noted that there was a little more lymphopenia in patients on lusvertikimab vs placebo, which is explained by the drug’s mechanism of action. However, “it was transient lymphopenia, without any infection and without any need to interrupt the treatment.”

Next, Bourreille said, we need to demonstrate the efficacy and the safety of the drug in the long term.

“There may be a place for lusvertikimab in patients with Crohn’s disease because the mechanism of action of IL-7 receptor antagonist would potentially have good efficacy in that disease too,” he added.

Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Greece, who comoderated the session, pointed out that the results supported further clinical development of lusvertikimab.

“As elevated mucosal IL-7/IL-7 [receptor] expression predicts refractoriness to currently used biologic therapies, it would be very interesting to see the potential of lusvertikimab as a treatment for patients who were exposed to advanced therapy or as part of combination therapeutics,” he said.

The study was funded by OSE Immunotherapeutics. Bourreille received funding from OSE Immunotherapeutics; grants from Takeda and Mauna Kea Technologies; and personal fees from AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. Bamias reported receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as adviser/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, Johnson & Johnson, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.

A version of this article appeared on Medscape.com.

BERLIN — Lusvertikimab, a first-in-class interleukin (IL)–7 receptor antagonist, demonstrated clinical and endoscopic efficacy in patients with moderate to severe ulcerative colitis (UC) in the 10-week induction period of a randomized, placebo-controlled, phase 2 clinical trial.

Lusvertikimab is unique in targeting the IL-7 receptor, a key player in immune-mediated inflammation.

“We have a new mode of action in ulcerative colitis,” with a strong safety profile, lead investigator, Arnaud Bourreille, MD, associate professor of gastroenterology from Nantes University Hospital, France, said in an interview.

“We achieved the primary endpoint” — improvement in the modified Mayo score (MMS) from baseline to week 10 — “for both the low dose and the high dose of lusvertikimab,” said Bourreille, who presented the findings at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress. “For us practitioners, this is very good news.”

Current treatment options for UC remain limited, especially for patients with an inadequate response to biologics or small molecules.

Overall, biologics are only effective in around half the patients, Bourreille noted. We need other treatments that have different mechanisms of action, as is the case with lusvertikimab.

The multicenter, double-blind CoTikiS study evaluated the IL-7 receptor antagonist in 136 adults with moderately to severely active UC (MMS, 4-9) and inadequate response to conventional therapies and/or failure to advanced therapies. Around 40% of the patients were exposed to one or more biologics.

The 50-week study had a 10-week induction period with two doses of lusvertikimab (450 and 850 mg), followed by a 24-week open-label extension, where patients received infusions of the high dose (850 mg) every 4 weeks, and a 16-week safety follow-up period free of treatment.

For the induction period, patients were randomized 1:1:1 to receive placebo (n = 49), 450 mg lusvertikimab (n = 35), or 850 mg lusvertikimab (n = 50) intravenously at weeks 0, 2, and 6. The diagnosis in two patients was modified to Crohn’s disease; therefore, they were not included.

In meeting the trial’s primary endpoint, lusvertikimab significantly reduced disease severity, compared with placebo, at week 10 in both dose groups separately and when pooled.

The MMS in the 450-mg group showed a difference of –1.16 points vs placebo (P = .019), whereas in the 850-mg group, the MMS showed a difference of –0.9 points vs placebo (P = .036). In the pooled group, the difference was –1.00 points vs placebo (P = .010).

The secondary endpoints of clinical remission and endoscopic remission also favored lusvertikimab for the pooled doses vs placebo, at 16% vs 4% (odds ratio [OR], 4.25; P = .066) and 25% vs 13% (OR, 2.33; P = .120), respectively.

For the other secondary endpoints, 32% achieved endoscopic improvement in the pooled group vs 13% in the placebo group (OR, 3.29; P = .027), and the mean score change in the UC Endoscopic Index of Severity was –1.35 for the pooled group vs –0.32 for the placebo group (P = .007).

Fecal calprotectin was reduced by 830 μg/g in the 450-mg group (P =.009), by 635 μg/g in the 850-mg group (P = .018), and 716 μg/g in the pooled group. It was increased by 189 μg/g in the placebo group (P = .004).

No safety concerns were reported.

Bourreille noted that there was a little more lymphopenia in patients on lusvertikimab vs placebo, which is explained by the drug’s mechanism of action. However, “it was transient lymphopenia, without any infection and without any need to interrupt the treatment.”

Next, Bourreille said, we need to demonstrate the efficacy and the safety of the drug in the long term.

“There may be a place for lusvertikimab in patients with Crohn’s disease because the mechanism of action of IL-7 receptor antagonist would potentially have good efficacy in that disease too,” he added.

Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Greece, who comoderated the session, pointed out that the results supported further clinical development of lusvertikimab.

“As elevated mucosal IL-7/IL-7 [receptor] expression predicts refractoriness to currently used biologic therapies, it would be very interesting to see the potential of lusvertikimab as a treatment for patients who were exposed to advanced therapy or as part of combination therapeutics,” he said.

The study was funded by OSE Immunotherapeutics. Bourreille received funding from OSE Immunotherapeutics; grants from Takeda and Mauna Kea Technologies; and personal fees from AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. Bamias reported receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as adviser/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, Johnson & Johnson, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.

A version of this article appeared on Medscape.com.