IBD & Intestinal Disorders

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

COPENHAGEN – A study of 260 patients with Crohn’s disease finds that vedolizumab led to significantly better clinical remission rates as compared with patients who were treated with anti–tumor necrosis factor (TNF) therapy.

The study was presented at the annual congress of the European Crohn’s and Colitis Organization by Wolfgang Mohl, MD, of the Center for Gastroenterology in Saarbrucken, Germany, who suggested this biologic, which is a monoclonal antibody, could possibly be used as a first-line treatment instead of as a second or third choice. Currently, TNF inhibitors are generally prescribed first.

“Compared to previous research clinical trials, this prospective 2-year real-world study comparing vedolizumab with anti-TNF showed that, in biologic-naive Crohn’s disease patients, remission rates at 2 years with vedolizumab were remarkably higher than with anti-TNF [therapy],” Dr. Mohl and colleagues wrote in the study abstract.

“Now we know vedolizumab is a good first-line drug and that patients can stay on it for a long time,” he said in an interview. “These data also suggest that we are wrong in thinking TNF inhibitors should be standard. I don’t think this belief holds true anymore.”

The study included 63 biologic-naive patients who were treated with vedolizumab and 197 patients who were treated with anti-TNF agents adalimumab (58.4%) and infliximab (41.6%).

After 2 years, approximately 83% of patients who were treated with vedolizumab were still receiving treatment, but only 56% of patients who received anti-TNF therapy were still undergoing therapy with either adalimumab or infliximab. After 2 years of treatment, 64.2% of patients who were treated with vedolizumab were in clinical remission, compared with 44.7% of patients who were treated with anti-TNF therapy. And, 62.5% of patients who were treated with vedolizumab were not receiving steroid treatment, compared with 41.6% of patients in the anti-TNF therapy group. This, Dr. Mohl said, was a statistically significant difference (P < .05).

“It is clinically relevant to achieve remission without steroids because this is hard to obtain,” he said. “Patients really don’t want to have to take steroids because they can experience lots of side effects including osteoporosis. It’s good to be in remission, but to be in steroid-free remission is so much better.”

Vedolizumab is a relatively new drug, compared with infliximab and adalimumab, which were approved by the Food and Drug Administration in 1998 and 2008, respectively. “We wanted real-world data to help us understand the pattern of outcomes outside of the clinical trial environment,” Dr. Mohl said.

From 45 treatment centers across Germany, researchers prospectively enrolled 1,200 biologic-naive and biologic-experienced patients with either Crohn’s disease or ulcerative colitis between 2017 and 2020 into the VEDOIBD study. This analysis was limited to 260 patients with Crohn’s disease.

In addition to a higher proportion of patients on vedolizumab continuing on treatment, compared with patients on anti–TNF inhibitor therapy, there was a significantly higher clinical remission rate with vedolizumab (64.2%), compared with anti-TNFi therapy (44.7%) after 2 years (P < .05). Researchers used a statistical method to determine the effect of 2-year maintenance in only those patients who responded to a 3-month induction, and they found a significantly better response in terms of clinical remission in patients on vedolizumab (88.6%), compared with anti-TNF inhibitors (45.8%) (P = .0001), and likewise in steroid-free remission with 86.8% for vedolizumab, compared with 44.1% for anti-TNF inhibitors (P < .001).

Dr. Mohl described his experience with vedolizumab in clinical practice. “Vedolizumab may take a little longer to work but then we don’t lose patients due to side effects, which we see more often with anti-TNF therapy,” he said, adding that around 60% of patients experience side effects but around 10% actually stop anti-TNF because of side effects.

“We often lose patients because they develop antidrug antibodies, but also due to escape mechanisms, as well as dermatological side effects including psoriasis which is really annoying for patients. We also find that anti-TNF drugs just stop working after 12-18 months, and then we need to use steroids which patients dislike,” he said.

Andreas Stallmach, MD, director of gastroenterology, Friedrich Schiller University Jena (Germany), described the findings as important.

“I see this as a really important real-world data study and to summarize, vedolizumab in Crohn’s disease is better than expected. The main explanation for the difference is due to loss of response in the anti-TNF group and this could be explained by the development of autoantibodies against anti-TNF drugs. Now, vedolizumab could be a first-line treatment in patients with Crohn’s disease, especially patients with risk factors for, or history of infections, of comorbidities,” he said.

As a modern monoclonal antibody, vedolizumab uses fewer autoantibodies, compared with infliximab, which is much older, Dr. Stallmach said. “If we combine infliximab with an immunosuppressant agent, such as azathioprine, then we can prevent autoantibody development and increase the efficacy and adherence rate, but with this comes the increased risk of infections and malignancies.”

Dr. Mohl receives research support from companies involved in making biologics for inflammatory bowel disease. Dr. Stallmach is on the advisory boards of most companies that make biologics, including Takeda, which sponsored this study.

* This article was updated March 10, 2023.

COPENHAGEN – A study of 260 patients with Crohn’s disease finds that vedolizumab led to significantly better clinical remission rates as compared with patients who were treated with anti–tumor necrosis factor (TNF) therapy.

The study was presented at the annual congress of the European Crohn’s and Colitis Organization by Wolfgang Mohl, MD, of the Center for Gastroenterology in Saarbrucken, Germany, who suggested this biologic, which is a monoclonal antibody, could possibly be used as a first-line treatment instead of as a second or third choice. Currently, TNF inhibitors are generally prescribed first.

“Compared to previous research clinical trials, this prospective 2-year real-world study comparing vedolizumab with anti-TNF showed that, in biologic-naive Crohn’s disease patients, remission rates at 2 years with vedolizumab were remarkably higher than with anti-TNF [therapy],” Dr. Mohl and colleagues wrote in the study abstract.

“Now we know vedolizumab is a good first-line drug and that patients can stay on it for a long time,” he said in an interview. “These data also suggest that we are wrong in thinking TNF inhibitors should be standard. I don’t think this belief holds true anymore.”

The study included 63 biologic-naive patients who were treated with vedolizumab and 197 patients who were treated with anti-TNF agents adalimumab (58.4%) and infliximab (41.6%).

After 2 years, approximately 83% of patients who were treated with vedolizumab were still receiving treatment, but only 56% of patients who received anti-TNF therapy were still undergoing therapy with either adalimumab or infliximab. After 2 years of treatment, 64.2% of patients who were treated with vedolizumab were in clinical remission, compared with 44.7% of patients who were treated with anti-TNF therapy. And, 62.5% of patients who were treated with vedolizumab were not receiving steroid treatment, compared with 41.6% of patients in the anti-TNF therapy group. This, Dr. Mohl said, was a statistically significant difference (P < .05).

“It is clinically relevant to achieve remission without steroids because this is hard to obtain,” he said. “Patients really don’t want to have to take steroids because they can experience lots of side effects including osteoporosis. It’s good to be in remission, but to be in steroid-free remission is so much better.”

Vedolizumab is a relatively new drug, compared with infliximab and adalimumab, which were approved by the Food and Drug Administration in 1998 and 2008, respectively. “We wanted real-world data to help us understand the pattern of outcomes outside of the clinical trial environment,” Dr. Mohl said.

From 45 treatment centers across Germany, researchers prospectively enrolled 1,200 biologic-naive and biologic-experienced patients with either Crohn’s disease or ulcerative colitis between 2017 and 2020 into the VEDOIBD study. This analysis was limited to 260 patients with Crohn’s disease.

In addition to a higher proportion of patients on vedolizumab continuing on treatment, compared with patients on anti–TNF inhibitor therapy, there was a significantly higher clinical remission rate with vedolizumab (64.2%), compared with anti-TNFi therapy (44.7%) after 2 years (P < .05). Researchers used a statistical method to determine the effect of 2-year maintenance in only those patients who responded to a 3-month induction, and they found a significantly better response in terms of clinical remission in patients on vedolizumab (88.6%), compared with anti-TNF inhibitors (45.8%) (P = .0001), and likewise in steroid-free remission with 86.8% for vedolizumab, compared with 44.1% for anti-TNF inhibitors (P < .001).

Dr. Mohl described his experience with vedolizumab in clinical practice. “Vedolizumab may take a little longer to work but then we don’t lose patients due to side effects, which we see more often with anti-TNF therapy,” he said, adding that around 60% of patients experience side effects but around 10% actually stop anti-TNF because of side effects.

“We often lose patients because they develop antidrug antibodies, but also due to escape mechanisms, as well as dermatological side effects including psoriasis which is really annoying for patients. We also find that anti-TNF drugs just stop working after 12-18 months, and then we need to use steroids which patients dislike,” he said.

Andreas Stallmach, MD, director of gastroenterology, Friedrich Schiller University Jena (Germany), described the findings as important.

“I see this as a really important real-world data study and to summarize, vedolizumab in Crohn’s disease is better than expected. The main explanation for the difference is due to loss of response in the anti-TNF group and this could be explained by the development of autoantibodies against anti-TNF drugs. Now, vedolizumab could be a first-line treatment in patients with Crohn’s disease, especially patients with risk factors for, or history of infections, of comorbidities,” he said.

As a modern monoclonal antibody, vedolizumab uses fewer autoantibodies, compared with infliximab, which is much older, Dr. Stallmach said. “If we combine infliximab with an immunosuppressant agent, such as azathioprine, then we can prevent autoantibody development and increase the efficacy and adherence rate, but with this comes the increased risk of infections and malignancies.”

Dr. Mohl receives research support from companies involved in making biologics for inflammatory bowel disease. Dr. Stallmach is on the advisory boards of most companies that make biologics, including Takeda, which sponsored this study.

* This article was updated March 10, 2023.

COPENHAGEN – A study of 260 patients with Crohn’s disease finds that vedolizumab led to significantly better clinical remission rates as compared with patients who were treated with anti–tumor necrosis factor (TNF) therapy.

The study was presented at the annual congress of the European Crohn’s and Colitis Organization by Wolfgang Mohl, MD, of the Center for Gastroenterology in Saarbrucken, Germany, who suggested this biologic, which is a monoclonal antibody, could possibly be used as a first-line treatment instead of as a second or third choice. Currently, TNF inhibitors are generally prescribed first.

“Compared to previous research clinical trials, this prospective 2-year real-world study comparing vedolizumab with anti-TNF showed that, in biologic-naive Crohn’s disease patients, remission rates at 2 years with vedolizumab were remarkably higher than with anti-TNF [therapy],” Dr. Mohl and colleagues wrote in the study abstract.

“Now we know vedolizumab is a good first-line drug and that patients can stay on it for a long time,” he said in an interview. “These data also suggest that we are wrong in thinking TNF inhibitors should be standard. I don’t think this belief holds true anymore.”

The study included 63 biologic-naive patients who were treated with vedolizumab and 197 patients who were treated with anti-TNF agents adalimumab (58.4%) and infliximab (41.6%).

After 2 years, approximately 83% of patients who were treated with vedolizumab were still receiving treatment, but only 56% of patients who received anti-TNF therapy were still undergoing therapy with either adalimumab or infliximab. After 2 years of treatment, 64.2% of patients who were treated with vedolizumab were in clinical remission, compared with 44.7% of patients who were treated with anti-TNF therapy. And, 62.5% of patients who were treated with vedolizumab were not receiving steroid treatment, compared with 41.6% of patients in the anti-TNF therapy group. This, Dr. Mohl said, was a statistically significant difference (P < .05).

“It is clinically relevant to achieve remission without steroids because this is hard to obtain,” he said. “Patients really don’t want to have to take steroids because they can experience lots of side effects including osteoporosis. It’s good to be in remission, but to be in steroid-free remission is so much better.”

Vedolizumab is a relatively new drug, compared with infliximab and adalimumab, which were approved by the Food and Drug Administration in 1998 and 2008, respectively. “We wanted real-world data to help us understand the pattern of outcomes outside of the clinical trial environment,” Dr. Mohl said.

From 45 treatment centers across Germany, researchers prospectively enrolled 1,200 biologic-naive and biologic-experienced patients with either Crohn’s disease or ulcerative colitis between 2017 and 2020 into the VEDOIBD study. This analysis was limited to 260 patients with Crohn’s disease.

In addition to a higher proportion of patients on vedolizumab continuing on treatment, compared with patients on anti–TNF inhibitor therapy, there was a significantly higher clinical remission rate with vedolizumab (64.2%), compared with anti-TNFi therapy (44.7%) after 2 years (P < .05). Researchers used a statistical method to determine the effect of 2-year maintenance in only those patients who responded to a 3-month induction, and they found a significantly better response in terms of clinical remission in patients on vedolizumab (88.6%), compared with anti-TNF inhibitors (45.8%) (P = .0001), and likewise in steroid-free remission with 86.8% for vedolizumab, compared with 44.1% for anti-TNF inhibitors (P < .001).

Dr. Mohl described his experience with vedolizumab in clinical practice. “Vedolizumab may take a little longer to work but then we don’t lose patients due to side effects, which we see more often with anti-TNF therapy,” he said, adding that around 60% of patients experience side effects but around 10% actually stop anti-TNF because of side effects.

“We often lose patients because they develop antidrug antibodies, but also due to escape mechanisms, as well as dermatological side effects including psoriasis which is really annoying for patients. We also find that anti-TNF drugs just stop working after 12-18 months, and then we need to use steroids which patients dislike,” he said.

Andreas Stallmach, MD, director of gastroenterology, Friedrich Schiller University Jena (Germany), described the findings as important.

“I see this as a really important real-world data study and to summarize, vedolizumab in Crohn’s disease is better than expected. The main explanation for the difference is due to loss of response in the anti-TNF group and this could be explained by the development of autoantibodies against anti-TNF drugs. Now, vedolizumab could be a first-line treatment in patients with Crohn’s disease, especially patients with risk factors for, or history of infections, of comorbidities,” he said.

As a modern monoclonal antibody, vedolizumab uses fewer autoantibodies, compared with infliximab, which is much older, Dr. Stallmach said. “If we combine infliximab with an immunosuppressant agent, such as azathioprine, then we can prevent autoantibody development and increase the efficacy and adherence rate, but with this comes the increased risk of infections and malignancies.”

Dr. Mohl receives research support from companies involved in making biologics for inflammatory bowel disease. Dr. Stallmach is on the advisory boards of most companies that make biologics, including Takeda, which sponsored this study.

* This article was updated March 10, 2023.

Children and young adults with inflammatory bowel disease (IBD) are about 2.5 times more likely to develop posttraumatic stress disorder (PTSD), almost twice as likely to report an eating disorder, and 1.5 times more likely to engage in self-harm, a new U.K. study suggests.

The retrospective, observational study of young people with IBD versus those without assessed the incidence of a wide range of mental health conditions in people aged 5-25 years.

“Anxiety and depression will not be a surprise to most of us. But we also saw changes for eating disorders, PTSD, and sleep changes,” said Richard K. Russell, MD, a pediatric gastroenterologist at the Royal Hospital for Sick Children, Edinburgh.

Dr. Russell presented the research at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.

The findings indicate an unmet need for mental health care for young patients with IBD, he said. “All of us at ECCO need to address this gap.”
 

Key findings

Dr. Russell and colleagues identified 3,898 young people diagnosed with IBD in the 10-year period Jan. 1, 2010, through Jan. 1, 2020, using the Optimum Patient Care Research Database, which includes de-identified data from more than 1,000 general practices across the United Kingdom. They used propensity score matching to create a control group of 15,571 people without IBD, controlling for age, sex, socioeconomic status, ethnicity, and health conditions other than IBD.

Median follow-up was about 3 years.

The cumulative lifetime risk for developing any mental health condition by age 25 was 31.1% in the IBD group versus 25.1% in controls, a statistically significant difference.

Compared with the control group, the people with incident IBD were significantly more likely to develop the following:

• PTSD.
• Eating disorders.
• Self-harm.
• Sleep disturbance.
• Depression.
• Anxiety disorder.
• ‘Any mental health condition.’

Those most are risk included males overall, and specifically boys aged 12-17 years. Those with Crohn’s disease versus other types of IBD were also most at risk.

In a subgroup analysis, presented as a poster at the meeting, Dr. Russell and colleagues also found that mental health comorbidity in children and young adults with IBD is associated with increased IBD symptoms and health care utilization, as well as time off work.

Children and young adults with both IBD and mental health conditions should be monitored and receive appropriate mental health support as part of their multidisciplinary care, Dr. Russell said.

Dr. Russell added that the study period ended a few months before the COVID-19 pandemic began, so the research does not reflect its impact on mental health in the study population.

“The number of children and young adults we’re seeing in our clinic with mental health issues has rocketed through the roof because of the pandemic,” he said.

Dr. Russell suggested that the organization create a psychology subgroup called Proactive Psychologists of ECCO, or Prosecco for short.
 

Clinical implications

The study is important for highlighting the increased burden of mental health problems in young people with IBD, said session comoderator Nick Kennedy, MD, a consultant gastroenterologist and chief research information officer with the Royal Devon University Healthcare NHS Foundation Trust in England.

Dr. Kennedy, who was not affiliated with the research, is also supportive of the idea of a psychological subgroup within ECCO.

The peak age for developing mental health disorders found by the study (12-17 years) “is a unique and very sensitive time,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in London.

“These results highlight the need for development of early screening psychiatric programs starting from time of diagnosis and continuing on periodic intervals to offer the best management plan for IBD patients, especially those with childhood-onset IBD,” said Dr. Mesilhy, who was not affiliated with the research.

Such programs would “improve the patient’s quality of life, protecting them from a lot of suffering and preventing the bad sequelae for these disorders,” said Dr. Mesilhy. “Moreover, we still need further studies to identify the most efficient monitoring and treatment protocols.”

Dr. Kennedy applauded the researchers for conducting a population-based study because it ensured an adequate cohort size and maximized identification of mental health disorders.

“It was interesting to see that there were a range of conditions where risk was increased, and that males with IBD were at particularly increased risk,” he added.

Researchers’ use of coded primary care data was a study limitation, but it was “appropriately acknowledged by the presenter,” Dr. Kennedy said.

The study was supported by Pfizer. Dr. Russell disclosed he is a consultant and member of a speakers’ bureau for Pfizer outside the submitted work. Dr. Kennedy and Dr. Mesilhy report no relevant financial relationships.

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

Children and young adults with inflammatory bowel disease (IBD) are about 2.5 times more likely to develop posttraumatic stress disorder (PTSD), almost twice as likely to report an eating disorder, and 1.5 times more likely to engage in self-harm, a new U.K. study suggests.

The retrospective, observational study of young people with IBD versus those without assessed the incidence of a wide range of mental health conditions in people aged 5-25 years.

“Anxiety and depression will not be a surprise to most of us. But we also saw changes for eating disorders, PTSD, and sleep changes,” said Richard K. Russell, MD, a pediatric gastroenterologist at the Royal Hospital for Sick Children, Edinburgh.

Dr. Russell presented the research at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.

The findings indicate an unmet need for mental health care for young patients with IBD, he said. “All of us at ECCO need to address this gap.”
 

Key findings

Dr. Russell and colleagues identified 3,898 young people diagnosed with IBD in the 10-year period Jan. 1, 2010, through Jan. 1, 2020, using the Optimum Patient Care Research Database, which includes de-identified data from more than 1,000 general practices across the United Kingdom. They used propensity score matching to create a control group of 15,571 people without IBD, controlling for age, sex, socioeconomic status, ethnicity, and health conditions other than IBD.

Median follow-up was about 3 years.

The cumulative lifetime risk for developing any mental health condition by age 25 was 31.1% in the IBD group versus 25.1% in controls, a statistically significant difference.

Compared with the control group, the people with incident IBD were significantly more likely to develop the following:

• PTSD.
• Eating disorders.
• Self-harm.
• Sleep disturbance.
• Depression.
• Anxiety disorder.
• ‘Any mental health condition.’

Those most are risk included males overall, and specifically boys aged 12-17 years. Those with Crohn’s disease versus other types of IBD were also most at risk.

In a subgroup analysis, presented as a poster at the meeting, Dr. Russell and colleagues also found that mental health comorbidity in children and young adults with IBD is associated with increased IBD symptoms and health care utilization, as well as time off work.

Children and young adults with both IBD and mental health conditions should be monitored and receive appropriate mental health support as part of their multidisciplinary care, Dr. Russell said.

Dr. Russell added that the study period ended a few months before the COVID-19 pandemic began, so the research does not reflect its impact on mental health in the study population.

“The number of children and young adults we’re seeing in our clinic with mental health issues has rocketed through the roof because of the pandemic,” he said.

Dr. Russell suggested that the organization create a psychology subgroup called Proactive Psychologists of ECCO, or Prosecco for short.
 

Clinical implications

The study is important for highlighting the increased burden of mental health problems in young people with IBD, said session comoderator Nick Kennedy, MD, a consultant gastroenterologist and chief research information officer with the Royal Devon University Healthcare NHS Foundation Trust in England.

Dr. Kennedy, who was not affiliated with the research, is also supportive of the idea of a psychological subgroup within ECCO.

The peak age for developing mental health disorders found by the study (12-17 years) “is a unique and very sensitive time,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in London.

“These results highlight the need for development of early screening psychiatric programs starting from time of diagnosis and continuing on periodic intervals to offer the best management plan for IBD patients, especially those with childhood-onset IBD,” said Dr. Mesilhy, who was not affiliated with the research.

Such programs would “improve the patient’s quality of life, protecting them from a lot of suffering and preventing the bad sequelae for these disorders,” said Dr. Mesilhy. “Moreover, we still need further studies to identify the most efficient monitoring and treatment protocols.”

Dr. Kennedy applauded the researchers for conducting a population-based study because it ensured an adequate cohort size and maximized identification of mental health disorders.

“It was interesting to see that there were a range of conditions where risk was increased, and that males with IBD were at particularly increased risk,” he added.

Researchers’ use of coded primary care data was a study limitation, but it was “appropriately acknowledged by the presenter,” Dr. Kennedy said.

The study was supported by Pfizer. Dr. Russell disclosed he is a consultant and member of a speakers’ bureau for Pfizer outside the submitted work. Dr. Kennedy and Dr. Mesilhy report no relevant financial relationships.

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

Children and young adults with inflammatory bowel disease (IBD) are about 2.5 times more likely to develop posttraumatic stress disorder (PTSD), almost twice as likely to report an eating disorder, and 1.5 times more likely to engage in self-harm, a new U.K. study suggests.

The retrospective, observational study of young people with IBD versus those without assessed the incidence of a wide range of mental health conditions in people aged 5-25 years.

“Anxiety and depression will not be a surprise to most of us. But we also saw changes for eating disorders, PTSD, and sleep changes,” said Richard K. Russell, MD, a pediatric gastroenterologist at the Royal Hospital for Sick Children, Edinburgh.

Dr. Russell presented the research at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.

The findings indicate an unmet need for mental health care for young patients with IBD, he said. “All of us at ECCO need to address this gap.”
 

Key findings

Dr. Russell and colleagues identified 3,898 young people diagnosed with IBD in the 10-year period Jan. 1, 2010, through Jan. 1, 2020, using the Optimum Patient Care Research Database, which includes de-identified data from more than 1,000 general practices across the United Kingdom. They used propensity score matching to create a control group of 15,571 people without IBD, controlling for age, sex, socioeconomic status, ethnicity, and health conditions other than IBD.

Median follow-up was about 3 years.

The cumulative lifetime risk for developing any mental health condition by age 25 was 31.1% in the IBD group versus 25.1% in controls, a statistically significant difference.

Compared with the control group, the people with incident IBD were significantly more likely to develop the following:

• PTSD.
• Eating disorders.
• Self-harm.
• Sleep disturbance.
• Depression.
• Anxiety disorder.
• ‘Any mental health condition.’

Those most are risk included males overall, and specifically boys aged 12-17 years. Those with Crohn’s disease versus other types of IBD were also most at risk.

In a subgroup analysis, presented as a poster at the meeting, Dr. Russell and colleagues also found that mental health comorbidity in children and young adults with IBD is associated with increased IBD symptoms and health care utilization, as well as time off work.

Children and young adults with both IBD and mental health conditions should be monitored and receive appropriate mental health support as part of their multidisciplinary care, Dr. Russell said.

Dr. Russell added that the study period ended a few months before the COVID-19 pandemic began, so the research does not reflect its impact on mental health in the study population.

“The number of children and young adults we’re seeing in our clinic with mental health issues has rocketed through the roof because of the pandemic,” he said.

Dr. Russell suggested that the organization create a psychology subgroup called Proactive Psychologists of ECCO, or Prosecco for short.
 

Clinical implications

The study is important for highlighting the increased burden of mental health problems in young people with IBD, said session comoderator Nick Kennedy, MD, a consultant gastroenterologist and chief research information officer with the Royal Devon University Healthcare NHS Foundation Trust in England.

Dr. Kennedy, who was not affiliated with the research, is also supportive of the idea of a psychological subgroup within ECCO.

The peak age for developing mental health disorders found by the study (12-17 years) “is a unique and very sensitive time,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in London.

“These results highlight the need for development of early screening psychiatric programs starting from time of diagnosis and continuing on periodic intervals to offer the best management plan for IBD patients, especially those with childhood-onset IBD,” said Dr. Mesilhy, who was not affiliated with the research.

Such programs would “improve the patient’s quality of life, protecting them from a lot of suffering and preventing the bad sequelae for these disorders,” said Dr. Mesilhy. “Moreover, we still need further studies to identify the most efficient monitoring and treatment protocols.”

Dr. Kennedy applauded the researchers for conducting a population-based study because it ensured an adequate cohort size and maximized identification of mental health disorders.

“It was interesting to see that there were a range of conditions where risk was increased, and that males with IBD were at particularly increased risk,” he added.

Researchers’ use of coded primary care data was a study limitation, but it was “appropriately acknowledged by the presenter,” Dr. Kennedy said.

The study was supported by Pfizer. Dr. Russell disclosed he is a consultant and member of a speakers’ bureau for Pfizer outside the submitted work. Dr. Kennedy and Dr. Mesilhy report no relevant financial relationships.

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars. 

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars. 

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars. 

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

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

COPENHAGEN – Half of patients with ileocecal Crohn’s disease who undergo ileocecal resection within a year of diagnosis remain off drug treatment 5 years post procedure, challenging the current paradigm of reserving surgery for complicated Crohn’s disease, show real-world data comparing outcomes of surgery with anti–tumor necrosis factor inhibitor (TNFi) therapy.

“These data show that resection of inflamed bowel in early ileocecal Crohn’s disease effectively resets the clock,” said Manasi Agrawal, MD, of the department of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, and a research associate with the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, who presented the findings at the annual congress of the European Crohn’s and Colitis Organisation. “These data are in accordance with the LIR!C study data and suggest that ileocecal resection could be a first-line therapeutic option in early ileal or ileocecal Crohn’s disease that could be discussed with our patients.”

While ileocecal resection is accepted as a therapeutic option in early Crohn’s disease, most clinicians reserve it for complicated disease that is refractory or intolerant to medication.

A radical shift in approach might be justified, said Jean-Frederic Colombel, MD, a study coinvestigator and gastroenterologist at Mount Sinai Hospital.

“These data can be transforming. It confirms that there may be a subset of patients with limited ileal Crohn’s disease that is uncomplicated and in whom surgery may be almost ‘curative’ because after follow-up there was no need for drug therapy. We need to reposition surgery as one possible option at diagnosis in patients with limited Crohn’s disease,” he said.

The 2017 LIR!C trial demonstrated comparable 1-year outcomes with ileocecal resection and anti-TNFi therapy in limited, nonstricturing ileocecal Crohn’s disease. A retrospective analysis of 5-year data from this trial, further reinforced ileocecal resection as a first-line option for limited Crohn’s disease, such that of those patients who underwent resection, 26% continued on anti-TNFi therapy, compared with 38% in those patients who took anti-TNFi therapy only. In addition, no patient in the resection group underwent subsequent surgery, whereas 48% of patients on anti-TNF underwent surgery.

Dr. Agrawal and coinvestigators decided that more conclusive, real-world data were needed and would help to determine whether ileocecal resection offered better patient outcomes than staying on anti-TNFi therapy.

The new findings are based on an analysis of 16,443 adults living with ileal Crohn’s disease and were diagnosed between 2003 and 2018. The data is based on an analysis of nationwide Danish registries. It included individuals who underwent

Ileocecal resection or received anti-TNF drugs within 1 year of diagnosis. Of the 16,443 patients diagnosed with Crohn’s disease over the study period, 1,279 had ileal or ileocecal disease and were included with 581 (3.5%) undergoing resection and 698 (4.2%) anti-TNFi index therapy.

Outcomes were compared between the two groups, and the proportions of individuals initiated on immunomodulator, anti-TNFi therapy, or no therapy at 5 years after their ileocecal resection were determined.

The primary outcome was CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. Crohn’s disease–related hospitalization, systemic corticosteroid use, Crohn’s disease–related surgery or perianal Crohn’s disease occurred in 273 versus 318 people in the ileocecal resection and anti-TNFi therapy groups respectively, equating to a 33% lower risk in the resection group. Of those patients who underwent ileocecal resection, 50.3% were on no treatment 5 years later; 47.5% and 17.1% were on immunomodulators and on anti-TNFi therapy respectively.

Resection was found to be associated with a statistically significant reduced risk of systemic corticosteroid use with an adjusted hazard ratio of 0.71 (95% confidence interval, 0.54-0.92). No statistically significant reduced risk was found for Crohn’s disease-related hospitalization (aHR, 0.79; 95% CI, 0.61-1.01) or perianal Crohn’s disease diagnosis (aHR, 0.70; 95% CI, 0.38-1.30). Adjustments were made for demographic and clinical variables, for example, age, sex, year of treatment, number of hospital contacts for an indication all in the year prior to index treatment.

In comparison with the proportion of resection patients at 5 years who were on no treatment, immunomodulators or anti-TNFi therapy, there are no data on the 5-year outcomes of those patients who began on anti-TNFi therapy, but patients typically continue unless they become intolerant or response starts to fail, Dr. Agrawal said.

Willem Bemelmen, MD, a colorectal surgeon from the University of Amsterdam who served as a moderator after the presentation said: “These results could lead to a paradigm shift in the management of patients with Crohn’s disease. Prior studies gave us early signals that surgery in Crohn’s disease might benefit the patients, but now with these larger scale data, with many patients, we might finally convince gastroenterologists to send patients in for early surgery.”

Dr. Agrawal, Dr. Bemelmen, and Dr. Colombel declared no relevant conflicts of interest.

This article was updated 3/7/23.

COPENHAGEN – Half of patients with ileocecal Crohn’s disease who undergo ileocecal resection within a year of diagnosis remain off drug treatment 5 years post procedure, challenging the current paradigm of reserving surgery for complicated Crohn’s disease, show real-world data comparing outcomes of surgery with anti–tumor necrosis factor inhibitor (TNFi) therapy.

“These data show that resection of inflamed bowel in early ileocecal Crohn’s disease effectively resets the clock,” said Manasi Agrawal, MD, of the department of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, and a research associate with the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, who presented the findings at the annual congress of the European Crohn’s and Colitis Organisation. “These data are in accordance with the LIR!C study data and suggest that ileocecal resection could be a first-line therapeutic option in early ileal or ileocecal Crohn’s disease that could be discussed with our patients.”

While ileocecal resection is accepted as a therapeutic option in early Crohn’s disease, most clinicians reserve it for complicated disease that is refractory or intolerant to medication.

A radical shift in approach might be justified, said Jean-Frederic Colombel, MD, a study coinvestigator and gastroenterologist at Mount Sinai Hospital.

“These data can be transforming. It confirms that there may be a subset of patients with limited ileal Crohn’s disease that is uncomplicated and in whom surgery may be almost ‘curative’ because after follow-up there was no need for drug therapy. We need to reposition surgery as one possible option at diagnosis in patients with limited Crohn’s disease,” he said.

The 2017 LIR!C trial demonstrated comparable 1-year outcomes with ileocecal resection and anti-TNFi therapy in limited, nonstricturing ileocecal Crohn’s disease. A retrospective analysis of 5-year data from this trial, further reinforced ileocecal resection as a first-line option for limited Crohn’s disease, such that of those patients who underwent resection, 26% continued on anti-TNFi therapy, compared with 38% in those patients who took anti-TNFi therapy only. In addition, no patient in the resection group underwent subsequent surgery, whereas 48% of patients on anti-TNF underwent surgery.

Dr. Agrawal and coinvestigators decided that more conclusive, real-world data were needed and would help to determine whether ileocecal resection offered better patient outcomes than staying on anti-TNFi therapy.

The new findings are based on an analysis of 16,443 adults living with ileal Crohn’s disease and were diagnosed between 2003 and 2018. The data is based on an analysis of nationwide Danish registries. It included individuals who underwent

Ileocecal resection or received anti-TNF drugs within 1 year of diagnosis. Of the 16,443 patients diagnosed with Crohn’s disease over the study period, 1,279 had ileal or ileocecal disease and were included with 581 (3.5%) undergoing resection and 698 (4.2%) anti-TNFi index therapy.

Outcomes were compared between the two groups, and the proportions of individuals initiated on immunomodulator, anti-TNFi therapy, or no therapy at 5 years after their ileocecal resection were determined.

The primary outcome was CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. Crohn’s disease–related hospitalization, systemic corticosteroid use, Crohn’s disease–related surgery or perianal Crohn’s disease occurred in 273 versus 318 people in the ileocecal resection and anti-TNFi therapy groups respectively, equating to a 33% lower risk in the resection group. Of those patients who underwent ileocecal resection, 50.3% were on no treatment 5 years later; 47.5% and 17.1% were on immunomodulators and on anti-TNFi therapy respectively.

Resection was found to be associated with a statistically significant reduced risk of systemic corticosteroid use with an adjusted hazard ratio of 0.71 (95% confidence interval, 0.54-0.92). No statistically significant reduced risk was found for Crohn’s disease-related hospitalization (aHR, 0.79; 95% CI, 0.61-1.01) or perianal Crohn’s disease diagnosis (aHR, 0.70; 95% CI, 0.38-1.30). Adjustments were made for demographic and clinical variables, for example, age, sex, year of treatment, number of hospital contacts for an indication all in the year prior to index treatment.

In comparison with the proportion of resection patients at 5 years who were on no treatment, immunomodulators or anti-TNFi therapy, there are no data on the 5-year outcomes of those patients who began on anti-TNFi therapy, but patients typically continue unless they become intolerant or response starts to fail, Dr. Agrawal said.

Willem Bemelmen, MD, a colorectal surgeon from the University of Amsterdam who served as a moderator after the presentation said: “These results could lead to a paradigm shift in the management of patients with Crohn’s disease. Prior studies gave us early signals that surgery in Crohn’s disease might benefit the patients, but now with these larger scale data, with many patients, we might finally convince gastroenterologists to send patients in for early surgery.”

Dr. Agrawal, Dr. Bemelmen, and Dr. Colombel declared no relevant conflicts of interest.

This article was updated 3/7/23.

COPENHAGEN – Half of patients with ileocecal Crohn’s disease who undergo ileocecal resection within a year of diagnosis remain off drug treatment 5 years post procedure, challenging the current paradigm of reserving surgery for complicated Crohn’s disease, show real-world data comparing outcomes of surgery with anti–tumor necrosis factor inhibitor (TNFi) therapy.

“These data show that resection of inflamed bowel in early ileocecal Crohn’s disease effectively resets the clock,” said Manasi Agrawal, MD, of the department of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, and a research associate with the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, who presented the findings at the annual congress of the European Crohn’s and Colitis Organisation. “These data are in accordance with the LIR!C study data and suggest that ileocecal resection could be a first-line therapeutic option in early ileal or ileocecal Crohn’s disease that could be discussed with our patients.”

While ileocecal resection is accepted as a therapeutic option in early Crohn’s disease, most clinicians reserve it for complicated disease that is refractory or intolerant to medication.

A radical shift in approach might be justified, said Jean-Frederic Colombel, MD, a study coinvestigator and gastroenterologist at Mount Sinai Hospital.

“These data can be transforming. It confirms that there may be a subset of patients with limited ileal Crohn’s disease that is uncomplicated and in whom surgery may be almost ‘curative’ because after follow-up there was no need for drug therapy. We need to reposition surgery as one possible option at diagnosis in patients with limited Crohn’s disease,” he said.

The 2017 LIR!C trial demonstrated comparable 1-year outcomes with ileocecal resection and anti-TNFi therapy in limited, nonstricturing ileocecal Crohn’s disease. A retrospective analysis of 5-year data from this trial, further reinforced ileocecal resection as a first-line option for limited Crohn’s disease, such that of those patients who underwent resection, 26% continued on anti-TNFi therapy, compared with 38% in those patients who took anti-TNFi therapy only. In addition, no patient in the resection group underwent subsequent surgery, whereas 48% of patients on anti-TNF underwent surgery.

Dr. Agrawal and coinvestigators decided that more conclusive, real-world data were needed and would help to determine whether ileocecal resection offered better patient outcomes than staying on anti-TNFi therapy.

The new findings are based on an analysis of 16,443 adults living with ileal Crohn’s disease and were diagnosed between 2003 and 2018. The data is based on an analysis of nationwide Danish registries. It included individuals who underwent

Ileocecal resection or received anti-TNF drugs within 1 year of diagnosis. Of the 16,443 patients diagnosed with Crohn’s disease over the study period, 1,279 had ileal or ileocecal disease and were included with 581 (3.5%) undergoing resection and 698 (4.2%) anti-TNFi index therapy.

Outcomes were compared between the two groups, and the proportions of individuals initiated on immunomodulator, anti-TNFi therapy, or no therapy at 5 years after their ileocecal resection were determined.

The primary outcome was CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. Crohn’s disease–related hospitalization, systemic corticosteroid use, Crohn’s disease–related surgery or perianal Crohn’s disease occurred in 273 versus 318 people in the ileocecal resection and anti-TNFi therapy groups respectively, equating to a 33% lower risk in the resection group. Of those patients who underwent ileocecal resection, 50.3% were on no treatment 5 years later; 47.5% and 17.1% were on immunomodulators and on anti-TNFi therapy respectively.

Resection was found to be associated with a statistically significant reduced risk of systemic corticosteroid use with an adjusted hazard ratio of 0.71 (95% confidence interval, 0.54-0.92). No statistically significant reduced risk was found for Crohn’s disease-related hospitalization (aHR, 0.79; 95% CI, 0.61-1.01) or perianal Crohn’s disease diagnosis (aHR, 0.70; 95% CI, 0.38-1.30). Adjustments were made for demographic and clinical variables, for example, age, sex, year of treatment, number of hospital contacts for an indication all in the year prior to index treatment.

In comparison with the proportion of resection patients at 5 years who were on no treatment, immunomodulators or anti-TNFi therapy, there are no data on the 5-year outcomes of those patients who began on anti-TNFi therapy, but patients typically continue unless they become intolerant or response starts to fail, Dr. Agrawal said.

Willem Bemelmen, MD, a colorectal surgeon from the University of Amsterdam who served as a moderator after the presentation said: “These results could lead to a paradigm shift in the management of patients with Crohn’s disease. Prior studies gave us early signals that surgery in Crohn’s disease might benefit the patients, but now with these larger scale data, with many patients, we might finally convince gastroenterologists to send patients in for early surgery.”

Dr. Agrawal, Dr. Bemelmen, and Dr. Colombel declared no relevant conflicts of interest.

This article was updated 3/7/23.

COPENHAGEN – Chronic pain in pediatric inflammatory bowel disease (IBD) is not associated with disease activity but has a significant impact on quality of life, including emotional well-being and social functioning, shows a study on chronic pain in children with IBD.

“A major finding of our small study was the impact of chronic pain on well-being and emotional health which was particularly significant in vulnerable children moving through adolescence towards adulthood,” said Dhamyanthi Thangarajah, MD, a consultant pediatric gastroenterologist at Chelsea and Westminster Hospital, London, in a presentation at the annual congress of the European Crohn’s and Colitis Organisation.

In the study of 41 children between 10 and 17 years old, chronic pain was found in 80% of participants who had established and extensive disease. Most participants had markers for fecal calprotectin, a sensitive marker for inflammation in the gastrointestinal tract, and others had Crohn’s disease and were prescribed biologics.

No relationship was found between chronic pain and IBD activity, but quality of life scores were negatively impacted in children with chronic pain.

“Moving forward, strategies should target screening for chronic pain in children with IBD and provide psychosocial interventions early on,” Dr. Thangarajah said. “We also need to understand more about internalizing pain and explore mood disorders.”

Many children with IBD also present with chronic abdominal pain, which was the impetus for conducting the study. “Essentially, we wondered whether this was a symptom of active disease, or were we missing something? In adult patients, chronic pain is prevalent, but in children we don’t necessarily screen for chronic pain, although it is part of active disease,” she said.

There is considerable patient and parental anxiety around the nature and origins of the chronic pain, Dr. Thangarajah said.

“We need to understand the prevalence and impact of chronic pain in children and adolescents, and as such we wanted to understand and characterize our cohort,” she said.

Dr. Thangarajah said clinicians tend to be very focused on disease activity and that screening for chronic pain is not usually carried out. “When we look at their clinical indices, the patients seem better, but the fact that it affects emotional health, and we don’t screen for it, means we need psychological help for these pediatric patients,” she said. “Patients need to be able to talk about their pain, and we need to understand if these children are having IBD-type symptoms, and this just isn’t asked about. It would be good to extend this study with a psychologist to understand more about this pain.”
 

How the study was conducted

The findings are based on the IMPACT III quality of life questionnaire for IBD. Chronic pain was defined as mild, moderate, or severe according to the van Korff scale.

“Patients had extensive and established disease, as expected in a pediatric cohort, the majority of whom were on immunosuppressant biologic drugs [64%-89%]. Among these patients, analgesic use was low, which is part of the education we give parents, and there was no opiate use in children, which differs from adults with IBD,” Dr. Thangarajah said.

A total of 33/41 (80%) of patients had chronic pain, and of these, abdominal chronic pain was most common in 30/33 (90%), joint pain was present in 2/33 (6%), and headache in 1/33, (3%). The majority 26/33 (79%) were on biologic agents, and analgesia use was low at 15/33 (45%). A total of 42% of children across the spectrum of chronic pain severity were on immunomodulators. Comorbidities were present in 42%-57% of patients with mild, and moderate-severe chronic pain respectively.

IBD disease activity in children with chronic pain was compared with those without chronic pain, as defined by Pediatric Crohn’s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), C-reactive protein (CRP), and faecal calprotectin. No difference was found.

Dr. Thangarajah highlighted the significantly lower quality of life score in children with chronic pain (69 and 51 in mild, and moderate-severe pain subgroups respectively, compared with 81 in those children without chronic pain, P < .05). Specifically, body image showed no difference between children with and without chronic pain (59-65 points across no pain, mild, moderate and severe chronic pain).

Chronic pain patients also commonly reported sleep disturbance with around 66% of patients with chronic pain, compared with around 11% in those without. Anemia was reported in 30% versus 21% respectively. However, nearly half of children with chronic pain had comorbidities 16/33 (48%), and 5/16 (31%) had diagnoses that may be associated with comorbid pain.
 

Psychosocial support within gastroenterology unavailable

Christine Norton, PhD, professor of nursing at Kings College London, also spoke at the conference on abdominal pain and the well-being of patients with IBD. She said that pain can still be a problem for some patients in remission from IBD.

“In adults we find pain is related to disease activity, however, 40%-50% of patients with IBD remission still report pain. Abdominal pain is dominant but it can be anywhere in the body. This is really poorly addressed in clinical consultations. It’s a ‘don’t ask, don’t tell’ situation where the nurse or doctor would do something if they could, but they just don’t ask the patients,” she said.

If patients volunteer the information that they still have pain during remission, it might get dismissed as irritable bowel syndrome (IBS), Dr. Norton said. “Some patients do fulfill these criteria for IBS, but it still needs to be managed. Here at ECCO, the focus is on getting patients into deep remission and inflammation under tight control, but what do we do with the jangling pain nerves although there’s nothing apparently triggering them, the gut-brain sensitivity – it’s so hard to live with it. They need support,” she said.

Dr. Norton said clinicians need a better way to validate chronic pain. “Sometimes people don’t feel believed, but even if the doctor believes them, they don’t know what to do anyway. There’s very few places with psychological support within the field of gastroenterology. Do we educate the gastroenterologist in this aspect? Do we develop the skills of IBD nurses?”

Dr. Thangarajah and Dr. Norton have no disclosures to declare.

COPENHAGEN – Chronic pain in pediatric inflammatory bowel disease (IBD) is not associated with disease activity but has a significant impact on quality of life, including emotional well-being and social functioning, shows a study on chronic pain in children with IBD.

“A major finding of our small study was the impact of chronic pain on well-being and emotional health which was particularly significant in vulnerable children moving through adolescence towards adulthood,” said Dhamyanthi Thangarajah, MD, a consultant pediatric gastroenterologist at Chelsea and Westminster Hospital, London, in a presentation at the annual congress of the European Crohn’s and Colitis Organisation.

In the study of 41 children between 10 and 17 years old, chronic pain was found in 80% of participants who had established and extensive disease. Most participants had markers for fecal calprotectin, a sensitive marker for inflammation in the gastrointestinal tract, and others had Crohn’s disease and were prescribed biologics.

No relationship was found between chronic pain and IBD activity, but quality of life scores were negatively impacted in children with chronic pain.

“Moving forward, strategies should target screening for chronic pain in children with IBD and provide psychosocial interventions early on,” Dr. Thangarajah said. “We also need to understand more about internalizing pain and explore mood disorders.”

Many children with IBD also present with chronic abdominal pain, which was the impetus for conducting the study. “Essentially, we wondered whether this was a symptom of active disease, or were we missing something? In adult patients, chronic pain is prevalent, but in children we don’t necessarily screen for chronic pain, although it is part of active disease,” she said.

There is considerable patient and parental anxiety around the nature and origins of the chronic pain, Dr. Thangarajah said.

“We need to understand the prevalence and impact of chronic pain in children and adolescents, and as such we wanted to understand and characterize our cohort,” she said.

Dr. Thangarajah said clinicians tend to be very focused on disease activity and that screening for chronic pain is not usually carried out. “When we look at their clinical indices, the patients seem better, but the fact that it affects emotional health, and we don’t screen for it, means we need psychological help for these pediatric patients,” she said. “Patients need to be able to talk about their pain, and we need to understand if these children are having IBD-type symptoms, and this just isn’t asked about. It would be good to extend this study with a psychologist to understand more about this pain.”
 

How the study was conducted

The findings are based on the IMPACT III quality of life questionnaire for IBD. Chronic pain was defined as mild, moderate, or severe according to the van Korff scale.

“Patients had extensive and established disease, as expected in a pediatric cohort, the majority of whom were on immunosuppressant biologic drugs [64%-89%]. Among these patients, analgesic use was low, which is part of the education we give parents, and there was no opiate use in children, which differs from adults with IBD,” Dr. Thangarajah said.

A total of 33/41 (80%) of patients had chronic pain, and of these, abdominal chronic pain was most common in 30/33 (90%), joint pain was present in 2/33 (6%), and headache in 1/33, (3%). The majority 26/33 (79%) were on biologic agents, and analgesia use was low at 15/33 (45%). A total of 42% of children across the spectrum of chronic pain severity were on immunomodulators. Comorbidities were present in 42%-57% of patients with mild, and moderate-severe chronic pain respectively.

IBD disease activity in children with chronic pain was compared with those without chronic pain, as defined by Pediatric Crohn’s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), C-reactive protein (CRP), and faecal calprotectin. No difference was found.

Dr. Thangarajah highlighted the significantly lower quality of life score in children with chronic pain (69 and 51 in mild, and moderate-severe pain subgroups respectively, compared with 81 in those children without chronic pain, P < .05). Specifically, body image showed no difference between children with and without chronic pain (59-65 points across no pain, mild, moderate and severe chronic pain).

Chronic pain patients also commonly reported sleep disturbance with around 66% of patients with chronic pain, compared with around 11% in those without. Anemia was reported in 30% versus 21% respectively. However, nearly half of children with chronic pain had comorbidities 16/33 (48%), and 5/16 (31%) had diagnoses that may be associated with comorbid pain.
 

Psychosocial support within gastroenterology unavailable

Christine Norton, PhD, professor of nursing at Kings College London, also spoke at the conference on abdominal pain and the well-being of patients with IBD. She said that pain can still be a problem for some patients in remission from IBD.

“In adults we find pain is related to disease activity, however, 40%-50% of patients with IBD remission still report pain. Abdominal pain is dominant but it can be anywhere in the body. This is really poorly addressed in clinical consultations. It’s a ‘don’t ask, don’t tell’ situation where the nurse or doctor would do something if they could, but they just don’t ask the patients,” she said.

If patients volunteer the information that they still have pain during remission, it might get dismissed as irritable bowel syndrome (IBS), Dr. Norton said. “Some patients do fulfill these criteria for IBS, but it still needs to be managed. Here at ECCO, the focus is on getting patients into deep remission and inflammation under tight control, but what do we do with the jangling pain nerves although there’s nothing apparently triggering them, the gut-brain sensitivity – it’s so hard to live with it. They need support,” she said.

Dr. Norton said clinicians need a better way to validate chronic pain. “Sometimes people don’t feel believed, but even if the doctor believes them, they don’t know what to do anyway. There’s very few places with psychological support within the field of gastroenterology. Do we educate the gastroenterologist in this aspect? Do we develop the skills of IBD nurses?”

Dr. Thangarajah and Dr. Norton have no disclosures to declare.

COPENHAGEN – Chronic pain in pediatric inflammatory bowel disease (IBD) is not associated with disease activity but has a significant impact on quality of life, including emotional well-being and social functioning, shows a study on chronic pain in children with IBD.

“A major finding of our small study was the impact of chronic pain on well-being and emotional health which was particularly significant in vulnerable children moving through adolescence towards adulthood,” said Dhamyanthi Thangarajah, MD, a consultant pediatric gastroenterologist at Chelsea and Westminster Hospital, London, in a presentation at the annual congress of the European Crohn’s and Colitis Organisation.

In the study of 41 children between 10 and 17 years old, chronic pain was found in 80% of participants who had established and extensive disease. Most participants had markers for fecal calprotectin, a sensitive marker for inflammation in the gastrointestinal tract, and others had Crohn’s disease and were prescribed biologics.

No relationship was found between chronic pain and IBD activity, but quality of life scores were negatively impacted in children with chronic pain.

“Moving forward, strategies should target screening for chronic pain in children with IBD and provide psychosocial interventions early on,” Dr. Thangarajah said. “We also need to understand more about internalizing pain and explore mood disorders.”

Many children with IBD also present with chronic abdominal pain, which was the impetus for conducting the study. “Essentially, we wondered whether this was a symptom of active disease, or were we missing something? In adult patients, chronic pain is prevalent, but in children we don’t necessarily screen for chronic pain, although it is part of active disease,” she said.

There is considerable patient and parental anxiety around the nature and origins of the chronic pain, Dr. Thangarajah said.

“We need to understand the prevalence and impact of chronic pain in children and adolescents, and as such we wanted to understand and characterize our cohort,” she said.

Dr. Thangarajah said clinicians tend to be very focused on disease activity and that screening for chronic pain is not usually carried out. “When we look at their clinical indices, the patients seem better, but the fact that it affects emotional health, and we don’t screen for it, means we need psychological help for these pediatric patients,” she said. “Patients need to be able to talk about their pain, and we need to understand if these children are having IBD-type symptoms, and this just isn’t asked about. It would be good to extend this study with a psychologist to understand more about this pain.”
 

How the study was conducted

The findings are based on the IMPACT III quality of life questionnaire for IBD. Chronic pain was defined as mild, moderate, or severe according to the van Korff scale.

“Patients had extensive and established disease, as expected in a pediatric cohort, the majority of whom were on immunosuppressant biologic drugs [64%-89%]. Among these patients, analgesic use was low, which is part of the education we give parents, and there was no opiate use in children, which differs from adults with IBD,” Dr. Thangarajah said.

A total of 33/41 (80%) of patients had chronic pain, and of these, abdominal chronic pain was most common in 30/33 (90%), joint pain was present in 2/33 (6%), and headache in 1/33, (3%). The majority 26/33 (79%) were on biologic agents, and analgesia use was low at 15/33 (45%). A total of 42% of children across the spectrum of chronic pain severity were on immunomodulators. Comorbidities were present in 42%-57% of patients with mild, and moderate-severe chronic pain respectively.

IBD disease activity in children with chronic pain was compared with those without chronic pain, as defined by Pediatric Crohn’s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), C-reactive protein (CRP), and faecal calprotectin. No difference was found.

Dr. Thangarajah highlighted the significantly lower quality of life score in children with chronic pain (69 and 51 in mild, and moderate-severe pain subgroups respectively, compared with 81 in those children without chronic pain, P < .05). Specifically, body image showed no difference between children with and without chronic pain (59-65 points across no pain, mild, moderate and severe chronic pain).

Chronic pain patients also commonly reported sleep disturbance with around 66% of patients with chronic pain, compared with around 11% in those without. Anemia was reported in 30% versus 21% respectively. However, nearly half of children with chronic pain had comorbidities 16/33 (48%), and 5/16 (31%) had diagnoses that may be associated with comorbid pain.
 

Psychosocial support within gastroenterology unavailable

Christine Norton, PhD, professor of nursing at Kings College London, also spoke at the conference on abdominal pain and the well-being of patients with IBD. She said that pain can still be a problem for some patients in remission from IBD.

“In adults we find pain is related to disease activity, however, 40%-50% of patients with IBD remission still report pain. Abdominal pain is dominant but it can be anywhere in the body. This is really poorly addressed in clinical consultations. It’s a ‘don’t ask, don’t tell’ situation where the nurse or doctor would do something if they could, but they just don’t ask the patients,” she said.

If patients volunteer the information that they still have pain during remission, it might get dismissed as irritable bowel syndrome (IBS), Dr. Norton said. “Some patients do fulfill these criteria for IBS, but it still needs to be managed. Here at ECCO, the focus is on getting patients into deep remission and inflammation under tight control, but what do we do with the jangling pain nerves although there’s nothing apparently triggering them, the gut-brain sensitivity – it’s so hard to live with it. They need support,” she said.

Dr. Norton said clinicians need a better way to validate chronic pain. “Sometimes people don’t feel believed, but even if the doctor believes them, they don’t know what to do anyway. There’s very few places with psychological support within the field of gastroenterology. Do we educate the gastroenterologist in this aspect? Do we develop the skills of IBD nurses?”

Dr. Thangarajah and Dr. Norton have no disclosures to declare.

COPENHAGEN – Vedolizumab (ENTYVIO) a monoclonal antibody drug, shows a higher overall 1- and 2-year persistence of use – the overall time that a patient stays on a medication – compared with two anti–tumor necrosis factor inhibitors (anti-TNFi) in both Crohn’s disease and ulcerative colitis, according to the first meta-analysis of their real-world effectiveness.

The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.

“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.

The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.

In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).

“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.

Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”

“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.  

Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”   

A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu.  “These findings suggested that alternative biologics with high effectiveness should be considered.”

Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.

Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”

As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.

Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).

Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).

In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.

In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.

In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.

Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”  

Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”

“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.

“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.” 

Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
 

COPENHAGEN – Vedolizumab (ENTYVIO) a monoclonal antibody drug, shows a higher overall 1- and 2-year persistence of use – the overall time that a patient stays on a medication – compared with two anti–tumor necrosis factor inhibitors (anti-TNFi) in both Crohn’s disease and ulcerative colitis, according to the first meta-analysis of their real-world effectiveness.

The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.

“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.

The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.

In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).

“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.

Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”

“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.  

Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”   

A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu.  “These findings suggested that alternative biologics with high effectiveness should be considered.”

Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.

Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”

As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.

Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).

Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).

In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.

In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.

In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.

Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”  

Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”

“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.

“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.” 

Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
 

COPENHAGEN – Vedolizumab (ENTYVIO) a monoclonal antibody drug, shows a higher overall 1- and 2-year persistence of use – the overall time that a patient stays on a medication – compared with two anti–tumor necrosis factor inhibitors (anti-TNFi) in both Crohn’s disease and ulcerative colitis, according to the first meta-analysis of their real-world effectiveness.

The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.

“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.

The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.

In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).

“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.

Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”

“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.  

Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”   

A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu.  “These findings suggested that alternative biologics with high effectiveness should be considered.”

Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.

Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”

As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.

Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).

Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).

In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.

In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.

In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.

Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”  

Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”

“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.

“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.” 

Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
 

COPENHAGEN – Mortality rate, length of hospital stay, and cost of hospitalization all drop significantly in patients with inflammatory bowel disease (IBD) concurrently using cannabis, shows a study that supports wider availability of the substance for specified medical use.

Inpatient mortality dropped by more than 70% in those patients concurrently using cannabis for another indication, compared with those not taking the drug, while total cost of hospitalization dropped by more than $11,000.

The findings were presented as a poster by Neethi Dasu, DO, PGY 6 Gastroenterology Fellow, at Jefferson Health Hospital, N.J., at the annual congress of the European Crohn’s and Colitis Organization. Dr. Dasu worked with coinvestigator Brian Blair, DO, FACOI, Gastroenterology Program Director, IBD specialist, at the same hospital.

“This study reveals substantial benefits of cannabis in the management of patients with IBD,” Dr. Dasu said. “Not only do patients spend less time in hospital, but they also have a decrease in mortality and hospital cost, which can be significant for patients with IBD, a chronic condition, that often burdens them with high health care spend.”

The researcher also highlighted that with annual U.S. health care spending on IBD having increased significantly in recent years, getting patients well and out of the hospital in a timely manner is key and that “cannabis might help in this aim.”

Cannabis use is legalized in some U.S. states for medical treatment of several chronic, debilitating disorders, especially cancer. Currently, there is no direct Food and Drug Administration approval for use for IBD. “Utilizing it would be considered off-label and investigational,” Dr. Dasu pointed out.

Patients report cannabis, as a pain control treatment, is effective for acute flares and chronic IBD, said Dr. Dasu. “It is an excellent agent for pain control that is not a narcotic, as with opioids, which can cause dependence and addiction. These could ultimately harm patients in the long term,” she addedin an interview. “Opioids can also cause drowsiness and side effects, which harm a person’s quality of life.”
 

Patients with IBD using cannabis concurrently

Dr. Dasu and her coresearchers aimed to see if outcomes including mortality and pain could be modified with “a very accessible and cost-efficient agent that does not cause long term addiction or adverse events.”

She added that previous studies had evaluated the clinical response in patients with IBD and concomitant cannabis use, but that their study was novel because it looked at inpatient outcomes as well as overall hospital cost.

Dr. Dasu and colleagues analyzed data over the years 2015-2019, from the Nationwide Inpatient Sample (NIS), a large publicly available all-payer inpatient care database, which encompasses approximately 7 million inpatient hospitalizations annually in the United States.

All included patients had IBD, either ulcerative colitis or Crohn’s disease, were aged 18 years and over, and used cannabis for a concurrent indication.

Odds ratios were calculated for in-hospital mortality, average length of hospital stay, and hospital charges, after adjusting for age, gender, race, primary insurance payer status, hospital type and size (number of beds), hospital region, hospital teaching status, and other demographic characteristics.

Of the 1,198,839 patients with IBD, 29,445 used cannabis for a different indication. Participants had an average age of 38.7 years.
 

Highly significant drop in mortality and hospital costs

Inpatient mortality shows a significant decrease of 72% (odds ratio, 0.28; confidence interval, 0.19-0.41, P < .0001) in those who concurrently used cannabis, compared with those who did not. Hospital length of stay also dropped by –0.17 days (95% CI, –0.35 to –0.01; P < .041), and this translated into a significant drop in the total cost of hospitalization from $39,309.00 (IBD without cannabis use) to $28,254.30 (IBD with cannabis use), resulting in an $11,054.70 savings (95% CI, –$13,681.15 to –$8,427.24; P < .0001).

As a chronic inflammatory disease, IBD involves immune dysregulation leading to symptoms of nausea, vomiting, bleeding, and abdominal pain; however, the pathophysiologic mechanism is not fully understood. She added that studies in mice had shown that cannabis acts via cannabinoid 1 and 2 receptors, located in the nervous system, to decrease pain, nausea, and vomiting. “Mechanisms of cannabis’s analgesic effect also involves inhibition of the release of neurotransmitters involved in pain and inflammation.”

Asked how she felt about the future for cannabis treatment in IBD, Dr. Dasu remarked that it would most likely require decriminalizing marijuana use on a federal level, although individual states currently offer exemptions.

“Further research should be done to evaluate the medical benefits of cannabis use in patients with IBD, with studies warranted to investigate the factors that may be driving these differences, as well warranted to investigations into the effect of cannabis on remission rates, rates of hospitalization, potential complications, and quality of life,” concluded Dr. Dasu.

Commenting on the study, Mary-Jane Williams, MD, a gastroenterology fellow at East Carolina University Health Medical Center, Greenville, N.C., told this news organization that the study was “a pleasant breath of information on the topic of cannabis use in IBD,” adding that providers often face questions about cannabis use from patients.

“Modulation of the endocannabinoid system ... plays a key role in the pathogenesis of IBD including pain control, limiting intestinal inflammation, and decreasing intestinal motility,” Dr. Williams said, adding that, “Its use in IBD has promising improvement in the therapeutic effect and overall quality of life.”

“This study highlights and supports substantial therapeutic effects of cannabis in the management of IBD patients, be it their pain control, improving nausea, appetite and sleep, remission rates, earlier time to recovery, shortened hospitalization and faster endoscopic improvement,” she pointed out, noting the need for further studies, but also that most organizations, including the Crohn’s and Colitis Foundation, support policies that facilitate the conduct of clinical research using objective parameters and the potential development of cannabinoid-based medications in the management of our patients with IBD.

Dr. Dasu, Dr. Blair, and Dr. Williams have declared no financial disclosures.

COPENHAGEN – Mortality rate, length of hospital stay, and cost of hospitalization all drop significantly in patients with inflammatory bowel disease (IBD) concurrently using cannabis, shows a study that supports wider availability of the substance for specified medical use.

Inpatient mortality dropped by more than 70% in those patients concurrently using cannabis for another indication, compared with those not taking the drug, while total cost of hospitalization dropped by more than $11,000.

The findings were presented as a poster by Neethi Dasu, DO, PGY 6 Gastroenterology Fellow, at Jefferson Health Hospital, N.J., at the annual congress of the European Crohn’s and Colitis Organization. Dr. Dasu worked with coinvestigator Brian Blair, DO, FACOI, Gastroenterology Program Director, IBD specialist, at the same hospital.

“This study reveals substantial benefits of cannabis in the management of patients with IBD,” Dr. Dasu said. “Not only do patients spend less time in hospital, but they also have a decrease in mortality and hospital cost, which can be significant for patients with IBD, a chronic condition, that often burdens them with high health care spend.”

The researcher also highlighted that with annual U.S. health care spending on IBD having increased significantly in recent years, getting patients well and out of the hospital in a timely manner is key and that “cannabis might help in this aim.”

Cannabis use is legalized in some U.S. states for medical treatment of several chronic, debilitating disorders, especially cancer. Currently, there is no direct Food and Drug Administration approval for use for IBD. “Utilizing it would be considered off-label and investigational,” Dr. Dasu pointed out.

Patients report cannabis, as a pain control treatment, is effective for acute flares and chronic IBD, said Dr. Dasu. “It is an excellent agent for pain control that is not a narcotic, as with opioids, which can cause dependence and addiction. These could ultimately harm patients in the long term,” she addedin an interview. “Opioids can also cause drowsiness and side effects, which harm a person’s quality of life.”
 

Patients with IBD using cannabis concurrently

Dr. Dasu and her coresearchers aimed to see if outcomes including mortality and pain could be modified with “a very accessible and cost-efficient agent that does not cause long term addiction or adverse events.”

She added that previous studies had evaluated the clinical response in patients with IBD and concomitant cannabis use, but that their study was novel because it looked at inpatient outcomes as well as overall hospital cost.

Dr. Dasu and colleagues analyzed data over the years 2015-2019, from the Nationwide Inpatient Sample (NIS), a large publicly available all-payer inpatient care database, which encompasses approximately 7 million inpatient hospitalizations annually in the United States.

All included patients had IBD, either ulcerative colitis or Crohn’s disease, were aged 18 years and over, and used cannabis for a concurrent indication.

Odds ratios were calculated for in-hospital mortality, average length of hospital stay, and hospital charges, after adjusting for age, gender, race, primary insurance payer status, hospital type and size (number of beds), hospital region, hospital teaching status, and other demographic characteristics.

Of the 1,198,839 patients with IBD, 29,445 used cannabis for a different indication. Participants had an average age of 38.7 years.
 

Highly significant drop in mortality and hospital costs

Inpatient mortality shows a significant decrease of 72% (odds ratio, 0.28; confidence interval, 0.19-0.41, P < .0001) in those who concurrently used cannabis, compared with those who did not. Hospital length of stay also dropped by –0.17 days (95% CI, –0.35 to –0.01; P < .041), and this translated into a significant drop in the total cost of hospitalization from $39,309.00 (IBD without cannabis use) to $28,254.30 (IBD with cannabis use), resulting in an $11,054.70 savings (95% CI, –$13,681.15 to –$8,427.24; P < .0001).

As a chronic inflammatory disease, IBD involves immune dysregulation leading to symptoms of nausea, vomiting, bleeding, and abdominal pain; however, the pathophysiologic mechanism is not fully understood. She added that studies in mice had shown that cannabis acts via cannabinoid 1 and 2 receptors, located in the nervous system, to decrease pain, nausea, and vomiting. “Mechanisms of cannabis’s analgesic effect also involves inhibition of the release of neurotransmitters involved in pain and inflammation.”

Asked how she felt about the future for cannabis treatment in IBD, Dr. Dasu remarked that it would most likely require decriminalizing marijuana use on a federal level, although individual states currently offer exemptions.

“Further research should be done to evaluate the medical benefits of cannabis use in patients with IBD, with studies warranted to investigate the factors that may be driving these differences, as well warranted to investigations into the effect of cannabis on remission rates, rates of hospitalization, potential complications, and quality of life,” concluded Dr. Dasu.

Commenting on the study, Mary-Jane Williams, MD, a gastroenterology fellow at East Carolina University Health Medical Center, Greenville, N.C., told this news organization that the study was “a pleasant breath of information on the topic of cannabis use in IBD,” adding that providers often face questions about cannabis use from patients.

“Modulation of the endocannabinoid system ... plays a key role in the pathogenesis of IBD including pain control, limiting intestinal inflammation, and decreasing intestinal motility,” Dr. Williams said, adding that, “Its use in IBD has promising improvement in the therapeutic effect and overall quality of life.”

“This study highlights and supports substantial therapeutic effects of cannabis in the management of IBD patients, be it their pain control, improving nausea, appetite and sleep, remission rates, earlier time to recovery, shortened hospitalization and faster endoscopic improvement,” she pointed out, noting the need for further studies, but also that most organizations, including the Crohn’s and Colitis Foundation, support policies that facilitate the conduct of clinical research using objective parameters and the potential development of cannabinoid-based medications in the management of our patients with IBD.

Dr. Dasu, Dr. Blair, and Dr. Williams have declared no financial disclosures.

COPENHAGEN – Mortality rate, length of hospital stay, and cost of hospitalization all drop significantly in patients with inflammatory bowel disease (IBD) concurrently using cannabis, shows a study that supports wider availability of the substance for specified medical use.

Inpatient mortality dropped by more than 70% in those patients concurrently using cannabis for another indication, compared with those not taking the drug, while total cost of hospitalization dropped by more than $11,000.

The findings were presented as a poster by Neethi Dasu, DO, PGY 6 Gastroenterology Fellow, at Jefferson Health Hospital, N.J., at the annual congress of the European Crohn’s and Colitis Organization. Dr. Dasu worked with coinvestigator Brian Blair, DO, FACOI, Gastroenterology Program Director, IBD specialist, at the same hospital.

“This study reveals substantial benefits of cannabis in the management of patients with IBD,” Dr. Dasu said. “Not only do patients spend less time in hospital, but they also have a decrease in mortality and hospital cost, which can be significant for patients with IBD, a chronic condition, that often burdens them with high health care spend.”

The researcher also highlighted that with annual U.S. health care spending on IBD having increased significantly in recent years, getting patients well and out of the hospital in a timely manner is key and that “cannabis might help in this aim.”

Cannabis use is legalized in some U.S. states for medical treatment of several chronic, debilitating disorders, especially cancer. Currently, there is no direct Food and Drug Administration approval for use for IBD. “Utilizing it would be considered off-label and investigational,” Dr. Dasu pointed out.

Patients report cannabis, as a pain control treatment, is effective for acute flares and chronic IBD, said Dr. Dasu. “It is an excellent agent for pain control that is not a narcotic, as with opioids, which can cause dependence and addiction. These could ultimately harm patients in the long term,” she addedin an interview. “Opioids can also cause drowsiness and side effects, which harm a person’s quality of life.”
 

Patients with IBD using cannabis concurrently

Dr. Dasu and her coresearchers aimed to see if outcomes including mortality and pain could be modified with “a very accessible and cost-efficient agent that does not cause long term addiction or adverse events.”

She added that previous studies had evaluated the clinical response in patients with IBD and concomitant cannabis use, but that their study was novel because it looked at inpatient outcomes as well as overall hospital cost.

Dr. Dasu and colleagues analyzed data over the years 2015-2019, from the Nationwide Inpatient Sample (NIS), a large publicly available all-payer inpatient care database, which encompasses approximately 7 million inpatient hospitalizations annually in the United States.

All included patients had IBD, either ulcerative colitis or Crohn’s disease, were aged 18 years and over, and used cannabis for a concurrent indication.

Odds ratios were calculated for in-hospital mortality, average length of hospital stay, and hospital charges, after adjusting for age, gender, race, primary insurance payer status, hospital type and size (number of beds), hospital region, hospital teaching status, and other demographic characteristics.

Of the 1,198,839 patients with IBD, 29,445 used cannabis for a different indication. Participants had an average age of 38.7 years.
 

Highly significant drop in mortality and hospital costs

Inpatient mortality shows a significant decrease of 72% (odds ratio, 0.28; confidence interval, 0.19-0.41, P < .0001) in those who concurrently used cannabis, compared with those who did not. Hospital length of stay also dropped by –0.17 days (95% CI, –0.35 to –0.01; P < .041), and this translated into a significant drop in the total cost of hospitalization from $39,309.00 (IBD without cannabis use) to $28,254.30 (IBD with cannabis use), resulting in an $11,054.70 savings (95% CI, –$13,681.15 to –$8,427.24; P < .0001).

As a chronic inflammatory disease, IBD involves immune dysregulation leading to symptoms of nausea, vomiting, bleeding, and abdominal pain; however, the pathophysiologic mechanism is not fully understood. She added that studies in mice had shown that cannabis acts via cannabinoid 1 and 2 receptors, located in the nervous system, to decrease pain, nausea, and vomiting. “Mechanisms of cannabis’s analgesic effect also involves inhibition of the release of neurotransmitters involved in pain and inflammation.”

Asked how she felt about the future for cannabis treatment in IBD, Dr. Dasu remarked that it would most likely require decriminalizing marijuana use on a federal level, although individual states currently offer exemptions.

“Further research should be done to evaluate the medical benefits of cannabis use in patients with IBD, with studies warranted to investigate the factors that may be driving these differences, as well warranted to investigations into the effect of cannabis on remission rates, rates of hospitalization, potential complications, and quality of life,” concluded Dr. Dasu.

Commenting on the study, Mary-Jane Williams, MD, a gastroenterology fellow at East Carolina University Health Medical Center, Greenville, N.C., told this news organization that the study was “a pleasant breath of information on the topic of cannabis use in IBD,” adding that providers often face questions about cannabis use from patients.

“Modulation of the endocannabinoid system ... plays a key role in the pathogenesis of IBD including pain control, limiting intestinal inflammation, and decreasing intestinal motility,” Dr. Williams said, adding that, “Its use in IBD has promising improvement in the therapeutic effect and overall quality of life.”

“This study highlights and supports substantial therapeutic effects of cannabis in the management of IBD patients, be it their pain control, improving nausea, appetite and sleep, remission rates, earlier time to recovery, shortened hospitalization and faster endoscopic improvement,” she pointed out, noting the need for further studies, but also that most organizations, including the Crohn’s and Colitis Foundation, support policies that facilitate the conduct of clinical research using objective parameters and the potential development of cannabinoid-based medications in the management of our patients with IBD.

Dr. Dasu, Dr. Blair, and Dr. Williams have declared no financial disclosures.